CN1520284A - Anorexic compsn. comprising calcium acetate - Google Patents

Abstract

The present invention provides an anorectic composition comprising calcium acetate in a form suitable for oral administration and absorption in the stomach and small intestine. The anorectic composition includes a flavor that masks the taste of calcium acetate, thus making the composition suitable for oral administration and absorption in the stomach and small intestine. The anorectic composition also includes a sweetener and pectin. The present invention also relates to a method of treating obesity comprising the step of administering said anorexic composition to a human in need thereof. Preferably the anorexic composition is administered in the form of a drink or food. The method comprises the step of administering to said person in need thereof a sufficient amount of the anorexic composition at least twice daily such that an effective amount of calcium acetate is administered to said person in the range of 3g to 7g, preferably 5g.

Description

Anorexic compositions comprising calcium acetate

The invention relates to an anorexia composition and its use in treating obesity.

The Applicant's South African Patent No. 97/7300 relates to an agent for the prevention or treatment of any of the following conditions in mammals: atherosclerosis, thrombosis, undesirably high levels of free radicals, undesirably long fibrin clots Clot lysis time, undesired clot properties of fibrin, undesirably high levels of free fatty acids and obesity and uses thereof. The medicament comprises calcium acetate in a pharmaceutically acceptable protective coating which prevents digestion and dissolution in the stomach and small intestine of the mammal, but is digested or dissolves in the colon of the mammal. This calcium acetate is released in the patient's colon, but not in the stomach and small intestine.

One disadvantage of calcium acetate in powder form is that it has a foul taste and is therefore not suitable for oral administration.

Another disadvantage of calcium acetate is that, in order to take a therapeutically effective dose of up to 15 tablets in tablet form, it must be taken orally 3 times a day. This is impractical and industrially useless.

The applicant has studied the method of preparing anorexic composition based on the above agents, and therefore the object of the present invention is to provide an anorectic composition and its use in the treatment of obesity which are improvements of the invention disclosed in the above patent.

According to a first aspect of the present invention there is provided an anorexic composition comprising calcium acetate in a form suitable for oral administration and absorption in the stomach and small intestine.

Also according to the present invention, the anorexic composition includes a flavoring agent that masks the taste of calcium acetate, thereby making the composition suitable for oral administration and absorption in the stomach and small intestine.

Calcium acetate can comprise from 54% to 89.9% based on the mass of the anorectic composition.

Flavoring agents may comprise from 5% to 20% based on the mass of the anorectic composition.

The anorectic composition may include a sweetener.

Sweeteners may comprise from 5% to 25% based on the mass of the anorectic composition.

The anorexic composition can include pectin.

Pectin may comprise 0.1%-1% based on the mass of the anorectic composition.

The anorectic composition may be in the form of a water soluble powder.

According to the second aspect of the present invention, there is provided a method for treating obesity, comprising the step of: administering the anorexic composition of the first aspect of the present invention to a person in need thereof.

The anorectic composition can be administered in the form of a drink or food.

The method may comprise the step of administering to said human in need thereof at least twice daily an amount of the anorexic composition sufficient to administer to the human an effective amount of 3g-7g calcium acetate.

Preferably an effective amount of 5 g of calcium acetate is administered to said human twice daily.

A preferred embodiment of the invention is now described by the following non-limiting examples:

Example 1

1. Method

1.1 Study Design

The main objective of this study was to determine the effect of the anorexic composition of the present invention on weight loss in obese subjects (calorie restricted diet). A double-blind, placebo-controlled design was chosen in which two parallel groups of subjects received the diet: supplemented with the anorexic composition and the micronutrient mix, or only with the micronutrient mix without the anorexic composition. A third group received meals supplemented with a placebo product for 12 weeks. By comparing the baseline and final values within each group, as well as the change in baseline and final values between groups in this design, and compared to that observed in the placebo group, the applicants were able to evaluate the anorexic composition and trace Effects of Nutrient Mixtures.

1.2 Participants

120 obese volunteers were recruited and screened in the applicant's metabolic unit. Use the following criteria:

Inclusion criteria: male or female; aged between 21-45; body mass index (BMI) > 27kg/m ² ; willing to comply with treatment;

Exclusion criteria: pregnancy; breastfeeding; any chronic disease; use of chronic medications and/or nutritional supplements.

The study protocol and procedures were explained to the volunteers, and 80 subjects meeting the criteria signed an information consent form. The 80 subjects (9 males and 71 females) were randomized into 3 groups and asked not to make major lifestyle changes during the 12-week study period, except those involving diet and complementary therapy. The mean age, weight, height and BMI of the three groups at baseline are shown in Tables 4.2 and 4.3. Due to the small number of male subjects, differences in responses between males and females were not evaluated.

1.3 Intervention

1.3.1 Meals

A calorie-restricted (fat-free) low-fat meal was given to each participant. The food types and serving sizes of the meals were selected to provide 5000-6000 kilojoules per day. The rationale for the diet and weight loss is explained to each subject. Food items on the subject's infrequently consumed meal list were replaced with low-fat alternatives. An analysis of nutrients selected from the daily intake of the meals administered to the women was prepared. This analysis showed that energy intake could even be reduced to below 5000 kJ with this diet, depending on the amount per serving. However, at this low energy intake, micronutrient intake would drop if micronutrient supplements were not used (not allowed in this study). The participating subjects were asked to accept the meal as much as possible. They will be told that if they do not lose weight, it will be a sign that they are not following the dietary rules. Following the low-fat principle and fewer servings of this diet, it is accepted that an energy deficit of at least 2000 kJ per day can be achieved, translating into a weight loss of 4.4 kg over a 12-week (84-day) period.

1.3.2 Supplements

In conjunction with this meal, the three groups were each given the supplement twice a day before two meals (most chose before breakfast and lunch). The supplement consists of a powder, 5ml (1 teaspoon) must be dissolved in a glass of water by stirring for a few seconds and then consumed immediately before meals. The composition of this supplement is shown in Table 1. Group 1 received a mixture of the micronutrient mix and the anorexic composition of the invention. Group 2 received a placebo supplement consisting of lactose, color and flavor. Group 3 received the same formulation as Group 1, except without the anorexic composition. A dose of 5ml twice per day allowed Group 1 to ingest 5g of the anorexic composition, providing an additional intake of 1265mg of calcium per day. 0.1%-1% pectin was added to Group 1 and Group 3 compositions.

Table 1 : Composition of Supplement in Daily 10 mL Dose Component Group 1 anorexic composition Group 2 placebo Group 3 Micronutrients calcium acetate 5g - - lactose - 5.5g 5g Micronutrient Blend Chromium (GTF) Vanadium Potassium 100μg50μg5mg - 100μg50μg5mg marine extract 200mg - 200mg choline 150mg - 150mg sweetener 0.36g 0.36g 0.36g Flavors and Colorants 0.54g 0.54g 0.54g Sorbitol 2g 2g 2g total capacity 5.00mL 5.00mL 5.00mL

1.4 Determination

For screening methods, subjects filled out demographic and medical history questionnaires. They weigh, measure height, and calculate body mass index. Baseline measurements were taken on the day that subjects in these 3 randomized groups received a calorie-restricted diet and received its supplements. These assays included anthropometric measurements, 24-hour dietary intake recall, and blood sampling to measure biochemical variables. This baseline measurement was repeated after 12 weeks to obtain final values. In addition, these subjects visit Applicants' metabolic unit once a week to be weighed, to monitor compliance with treatment, and to receive their supplements. The available methods for determining all these variables and the normal range/cut point (cut point) are summarized in Table 2.

Table 2 : Methods used to determine variables: baseline and final values variable method normal range Anthropometric measurements: height (m) Rangefinder, no shoes, correct position weight(kg) Precision Health Scale; indoor wear only BMI (kg/m ² ) Calculated in kg/m ² 18-25 Waist (cm) Determination of non-stretchable plastic tape Hips (cm) "" Upper arm circumference (cm) "" blood pressure Tycos Adult Human Blood Pressure Monitor 120/80mmHg body temperature Braun Thermal Scan Ear Thermometer 37°C Demographics Questionnaire meal data 24-hour recall questionnaire blood sample Venous blood from the cephalic vein with butterfly (21G) and syringe serum prepared from clotted blood plasma Blood preparation containing citrate (1:4) Hemoglobin (mmol/L) Cyanmethaemoglobin colorimetric method using whole blood 8.7-11.2 males 7.5-9.9 females Hematocrit (%) centrifugation, using heparinized blood 39-49 males 33-44 females Plasma fibrinogen (g/L) Clauss, ACL 200 Law 250-300 Serum total cholesterol (mmol/L) DAX Atlas: Enzymatic Colorimetry <4.0 LDL-cholesterol (mmol/L) calculate <3.4 HDL-cholesterol (mmol/L) DAX Atlas: Enzymatic Colorimetry >1.0 Triglyceride (mmol/L) DAX Atlas: Enzymatic Colorimetry 0.8-1.50

1.5 Statistical Analysis

These data were computerized, cleaned (dual monitoring) and analyzed using the program SPSS (version 9). Baseline and final values for each group were compared using a paired-samples test. Due to the small size of these groups, a nonparametric measure, the Kruskal-Wallis test, was used to compare the change from baseline to final value between each group.

1.6 Ethical considerations

The Ethics Committee of the Applicant approved the study (EthicsCommittee number OOM22). All subjects signed written consent forms. Those who volunteered but did not meet the inclusion criteria opted in to the Lipid Clinic of the Applicant in the Metabolic Unit for screening of serum liposomes and dietary advice.

2. Results

2.1 Object

Table 3 shows that of the 80 subjects recruited, 5 (all female) dropped out (3 from Group 1 and 1 from each of the other two groups). Two subjects in Group 1 were found unable to accept the meal; the other 3 had other unrelated medical issues that prevented them from further participation. Adherence (acceptability) to meals and products was noted during and at the end of the study. While still being "blinded" to these treatments, subjects who showed that they were not compliant with the product were selected as "non-compliant". Table 3 shows that in Group 1 there were 10 non-compliants, in Group 2 there were 2, and in Group 3 there were 4.

Table 3 : Number of Participating Objects Group 1 Group 2 Group 3 total Total number of enlisted and randomized 27 26 27 80 quit* 3 1 1 5 Disobedient # 10 2 4 16 Submissive 14 twenty three twenty two 59

Group 1: Anorexic compositions

Group 2: placebo

Group 3: Micronutrient Blend, (Micronutrient Blend without Calcium Acetate)

Table 4 shows that the mean ages of the 3 groups were not significantly different, nor were the ages of the compliant and non-compliant in each group.

Table 4 : Age and height of compliant and non-compliant subjects in each group variable Group 1 Group 2 Group 3 C NC C NC C NC number of objects 14 10 twenty three 2 twenty two 4 age (year) 37.3±8.2 33.1±8.7 36.2±8.1 38.5±9.2 37.5±6.6 41.7±4.7 height (cm) 1.66±0.11 1.64±0.62 1.64±0.84 1.72±0.82 1.67±0.73 1.66±0.89

C = Compliant (see below)

NC = Non-Conforming (see below)

Group 1: anorexic composition + meal

Group 2: placebo + meal

Group 3: Micronutrient Mix + Meal

2.2 Changes in body weight and body mass index

Table 5 shows that mean body weight and body mass index (BMI) were significantly lower in compliant subjects in all 3 groups. Table 5 also shows that Group 1 lost 9.2 kg, which was significantly greater than Group 2 (5.8 kg lost). The BMI of group 1 decreased by 3.3 kg/m ² , which was significantly greater than that of group 2 (2.1 kg/m ² ) and group 3 (1.9 kg/m ² ). As expected, noncompliant individuals in each group lost less weight than compliant individuals.

Table 5 : Weight and body mass index of compliant and non-compliant subjects variable Group 1 Group 2 group 3 C NC C NC C NC number of objects 14 10 twenty three 2 twenty two 4 Body weight (kg): baseline SD 97.1 ^A ±25.6 91.4±17.3 92.7 ^b ±18.6 84.8±17.9 ^89.8c ±13.7 86.5±24.0 Body weight (kg): final SD 87.9 ^A ±22.2 89.8±17.5 86.9 ^b ±18.0 82.5±21.9 ^84.3c ±13.4 83.7±23.1 weight change ^9.2g 1.6 ^5.8g 2.3 5.5 2.8 BMI (kg/m ² ): baseline SD ^34.8d ±6.7 33.7±4.7 ^34.3e ±15.7 28.6±3.0 32.1 ^f ±5.2 31.2±7.5 BMI (kg/m ² ): final SD ^31.5d ±5.9 33.1±4.6 ^32.2e ±5.8 27.8±4.5 30.2 ^f ±5.3 30.3±7.3 BMI change 3.3 ^h1 0.6 2.1 ^hours 0.8 1.9 ⁱ 0.9

C = Compliant (see below)

NC = Non-Conforming (see below)

BMI = body mass index

SD = standard deviation

a, b, c... with the same sign are significantly different (p≤0.05):

Within groups, paired-samples tests; variation between groups, Kruskal-Wallis test (nonparametric)

Group 1: anorexic composition + meal

Group 2: placebo + meal

Group 3: Micronutrient Mix + Meal

2.3 Changes in body circumference

Table 6 shows that weight change in submissives was accompanied by significant reductions in waist, hip, thigh, and mid-upper arm circumference in all 3 groups. With the exception of hip and mid-upper arm circumference in Group 2, these decreases were larger in Group 1, although less pronounced.

Table 6 : Body size of compliant and non-compliant subjects variable First group Second Group The third group C NC C NC C NC number of objects 14 10 twenty three 2 twenty two 4 Waist circumference (cm): baseline SD 98.2 ^a 18.9 96.8±23.2 95.1±15.3 96.5 ^b ±10.6 94.0±13.8 89.7±5.7 Waist circumference (cm): Final SD 92.2 ^A ±17.3 91.5±16.7 89.6±13.8 94.0 ^b ±11.3 88.8±11.1 87.0±7.2 Waist changes 6.0 5.3 5.5 2.5 5.2 2.7 Hip circumference (cm): baseline SD ^117.2c ±10.8 115.4±8.4 ^118.3d ±2.8 110.0±2.8 ^112.8e ±7.7 113.0±14.9 Hips (cm): Final SD ^111.4c ±9.5 113.6±7.6 ^112.6d ±11.1 105.5±0.71 ^108.5e ±8.2 110.0±17.3 hip change 5.8 1.8 5.7 4.5 4.3 3.0 Thigh circumference (cm): baseline SD 66.6 ^f ±9.1 68.1±4.9 65.8 ^g ±6.0 58.5±2.1 64.1 ^h ±3.9 68.0±7.9 Thigh circumference (cm): Final SD 58.5 ^f ±5.1 62.9±3.9 60.4 ^g ±6.5 55.5±0.7 58.1 ^h ±4.8 64.7±8.1 changes in thigh circumference 8.1 5.2 5.4 3.0 6.0 3.3 Upper middle hip circumference (cm): baseline SD 33.1 ^l ±13.9 32.4±2.5 35.5 ^l ±7.8 32.0±4.2 ^32.9k ±2.5 33.0±3.0 Upper middle hip circumference (cm): Final SD 30.6 ^l ±3.0 30.5±2.4 31.6 ^l ±3.6 30.5±5.0 ^30.9k ±2.6 30.7±3.8 Upper middle hip changes 2.5 1.9 3.9 1.5 2.0 2.3

C = Compliant (see below)

NC = Non-Conforming (see below)

BMI = body mass index

SD = standard deviation

a, b, c... with the same sign are significantly different (p≤0.05):

Within groups, paired-samples tests; variation between groups, Kruskal-Wallis test (nonparametric)

Group 1: anorexic composition + meal

Group 2: placebo + meal

Group 3: Micronutrient Mix + Meal

2.4 Changes in hematological variables

Table 7 shows the changes in hemoglobin, hematocrit and plasma fibrinogen. Submissives in all 3 groups showed a significant decrease in hemoglobin, although mean final values remained within the normal range of 8.7-11.2 mmol/L (men) and 7.5-9.9 mmol/L (women).

Hematocrit decreased significantly in Groups 1 and 2. During the baseline period, Group 2 values decreased more significantly than Group 1. However, the changes of 1.1 and 4.0 mmol/L for the compliant were not statistically significant among the 3 groups.

Table 7 also shows changes in plasma fibrinogen. There was a small but statistically significant increase in plasma fibrinogen (0.13 and 0.12 g/L) in the compliant subjects of Groups 1 and 2. Non-compliants in both groups had very small and insignificant decreases.

Subjects in Group 3 adhering to the product had a small but significant decrease (0.05 g/L) in plasma fibrinogen.

Table 7 : Hematological variables for compliant and non-compliant subjects in each group variable First group Second Group The third group C NC C NC C NC number of objects 14 10 twenty three 2 twenty two 4 Hemoglobin mmol/L baseline SD 10.2 ^a ±1.2 10.3±1.7 9.6 ^b ±1.1 9.6±0.1 ^9.8c ±1.6 9.9±0.5 Hemoglobin mmol/L final SD 9.3 ^a ±1.3 9.0±1.0 9.0 ^b ±1.1 10.1±1.4 8 ^8c ±1.1 8.6±1.8 hemoglobin changes 0.9 1.3 0.6 0.5↑ 1.0 1.3 Hematocrit %: % Baseline SD 43.4±3.7 43.6±4.1 41.8 ^de ±2.1 42.5±3.5 43.7 ^fe ±3.2 42.0±1.0 Hematocrit %: Final SD 42.3±3.7 40.9±4.6 ^39.6d ±4.5 42.0±2.8 39.7 ^f ±4.5 hematocrit changes 1.1 2.7 2.2 0.5 4.0 Plasma fibrinogen g/L: baseline SD 3.69 ^g ±0.63 3.57±0.80 3.52h±0.72 3.68±0.26 3.51 ^l ±0.87 3.54±1.15 Plasma fibrinogen g/L: Final SD 3.82 ^g ±1.11 3.54±0.74 3.64 ^h ±0.74 3.62±0.42 3.46 ^l ±0.89 3.58±0.70 Changes in plasma fibrinogen 0.13↑ 0.03↓ 0.12↑ 0.06↓ 0.05↓ 0.04↑

- cannot get value

C = Compliant (see below)

NC = Non-Conforming (see below)

BMI = body mass index

SD = standard deviation

a, b, c... with the same sign are significantly different (p≤0.05):

Within groups, paired-samples tests; variation between groups, Kruskal-Wallis test (nonparametric)

Group 1: anorexic composition + meal

Group 2: placebo + meal

Group 3: Micronutrient Mix + Meal

2.5 Changes in serum liposomes and lipoproteins

Table 8 shows changes in serum total cholesterol, LDL- and HDL-cholesterol and serum triglycerides. Although none of these changes were statistically significant within or between the compliant groups, it was noted that there were slight decreases in total and LDL-cholesterol. HDL-cholesterol did not change. However, serum triglycerides in Group 1 showed an increase from 1.19 to 1.68 mmol/L. This increase was not statistically significant, but a clinically significant increase could be present in some compliant subjects.

Table 8 : Mean (standard deviation) nutrient intake of compliant and non-compliant subjects in each group* Nutrients, (units) and RDA First group Second Group The third group C NC C NC C NC Energy (kJ) Baseline Final 7413±21785239±2602 5700±28905178±2833 7371±28764866±2030 9974±43414922±1445 6719±30105204±2626 7566±50647273±3680 Total Protein (g) Baseline Final 63.4±22.357.5±23.2 57.3±28.356.5±30.3 66.8±30.251.1±17.4 78.6±45.753.3±19.0 62.5±23.855.1±20.5 81.5±45.965.0±17.8 Vegetable Protein (g) Baseline Final 19.4±5.018.4±8.4 15.6±5.915.0±9.5 21.1±11.914.2±8.4 19.1±10.312.3±3.3 18.4±7.915.4±5.2 16 9±12.021.8±7.4 Total Fat (g) Baseline Final 65.3±26.246.8±30.0 50.0±34.243.8±29.4 61.0±25.337.7±24.5 77.2±53.546.1±31.7 59.2±39.842.3±34.9 78.9±59.262.9±28.6 SATFAT(g) Baseline Final 22.8±9.414.6±9.7 18.0±11.316.7±11.9 21.4±9.814.0+9.4 24.9±16.116.6±7.8 19.5±12.615.3±12.4 35.9±27.719.0±5.9 MUFAT(g) Baseline Final 22.1±9.614.5±8.8 16.3±11.414.1±10.7 20.4±9.712.0±7.9 28.0±19.317.6±16.2 20.1±13.314.3±13.3 25.5±20.320.2±4.7 PUFAT(g) Baseline Final 13.8±7.510.1±5.9 11.3±9.69.0±6.1 13.6±9.48.1±7.0 16.9±13.78.3±5.9 12.2±12.88.5±8.7 10.4±7.318.7±18.7 Cholesterol (mg) Baseline Final 287±213162±106 175±135205±202 206±130158±117 290±123140±83 205±181171±149 241±127315±84 Alcohol (g) Baseline Final 4.8±12.93.3±8.1 3.3±10.41.8±5.7 2.8±10.32.4±6.4 21.6±30.6- 2.69±9.04.4±8.6 7.5±13.0- Carbohydrates (g) Baseline Final 206±61129.9±68.5 152±64138.2±89.0 212±101137±57.7 289±136124.0±3.8 183±79140.5±65.6 160±128212.4±136.1 Added Sugar (g) Baseline Final 55.3±38.212.8±20.8 22.6±19.920.6±22.7 50.3±50.42.0±23.1 107.2±1.523.4±22.7 42.1±37.524.9±25.6 24.7±30.351.9±72.6 Total Fiber (g) Baseline Final 17.2±3.813.2±6.5 11.5±5.011.5±6.8 17.2±9.012.3±5.3 15.8±9.712.3±7.1 16.7±8.411.0±5.1 19.6±13.913.8±6.0 Calcium (mg) Baseline Final 576±214496±495 422±239426±292 640±342433±290 1123±1276199±72 516±329458±169 873±743504±197 Iron (mg) Baseline Final Magnesium (mg) 12.3±5.110.9±10.7 8.7±5.08.8±3.9 9.0±2.97.8±3.8 10.9±5.06.3±0.3 12.4±6.68.6±4.1 10.0±4.59.0±2.1 baseline final 275.5±74.1224.5±82.3 192.6±87.3179.0±75.4 259.0±78.1198.3±75.4 310.0±215.0157.0±26.9 243.7±102.7200.7±59.1 323.3±190.1244.7±49 Phosphorus (mg) Baseline Final 941.9±245.7847.5±413.9 736.6±381.7787.1±388.3 1036.1±431.5747.3±302.7 1358±1067.7622.0±60.8 907.5±389.8772.7±229.3 1255.0±907.1901.0±188.6 Nutrients, (units) and RDA Group 1 Group 2 group 3 C NC C NC C NC Potassium (mg) Baseline Final 2594±865.91980.4±464.8 1962.7±879.31590.7±657.4 2492±692.51958.6±851.3 3866.0±2723.81739.5±221.3 2291.4±1094.61940.6±656.0 3045.7±1764.52329.0±595.5 Sodium (mg) Baseline Final 1713.0±674.11253.5±801.3 1231.0±703.01360.3±872.7 1492.4±848.7973.1±633.2 1710.0±1298.3639.0±396.0 1497.7±838.31225.1±644.2 1758.3±1765.21029.3±323.6 Zinc (mg) Baseline Final 8.9±.3.27.0±.3.6 7.5±4.07.6±4.6 8.6±3.27.5±4.3 13.2±9.56.1±1.2 8.5±2.97.3±2.8 11.7±8.29.2±2.1 Copper (mg) Baseline Final 1.3±0.30.9±0.4 0.9±0.41.2±1.1 1.3±0.60.9±0.3 1.2±0.40.8±0.01 1.1±0.41.0±0.7 1.4±1.21.1±0.4 Chromium (mg) Baseline Final 57.6±48.253.1±19.0 47.3±36.045.5±41.8 58.7±33.843.2±27.0 142.5±65.046.5±49.6 53.5±25.743.2±31.1 61.0±46.251.5±22.1 Selenium (mg) Baseline Final 62.9±52.640.8±23.5 27.8±19.448.6±39.5 52.3±37.627.2±13.4 42.3±5.026.5±11.2 42.9±30.643.2±35.2 49.7±33.538.0±16.1 Iodine (mg) Baseline Final 48.9±30.033.0±12.9 32.0±19.032.8±24.9 35.9±15.631.0±15.1 60.0±2.817.5±12.0 37.1±27.029.3±21.2 52.0±38.443.7±11.0 Vitamin A(RE) Baseline Final 1240.9±1535.5565.8±615.7 346.5±262.2877.4±1186.4 1308.3±1396.7943.1±1493.1 787.0±784.91405.0±1158.2 1009.5±1457.3452.2±633.9 1866.7±1574.6257.3±156.5 Thiamine Baseline Ultimate 1.0±0.30.9±0.5 0.8±0.40.8±0.6 0.9±0.50.8±0.5 1.2±0.90.7±0.3 1.0±0.40.8±0.6 1.2±1.00.9±0.1 Riboflavin Baseline Final 1.5±1.01.0±0.8 0.9±0.71.1±0.9 1.1±0.51.0±0.6 1.6±1.30.6±0.07 1.2±0.71.0±0.5 1.5±1.11.0±0.2 Niacin Baseline Ultimate 18.9±6.919.3±10.2 16.4±9.014.7±7.0 17.1±7.915.1±8.2 15.5±5.218.0±9.1 19.3±10.915.2±7.2 15.3±8.315.3±4.4 Vitamin B12 Baseline Final 4.2±2.92.3±1.6 2.4±1.67.8±10.8 3.3±3.32.4±1.4 2.9±1.41.9±1.5 2.9±1.44.3±5.3 3.7±1.93.4±0.7 Vitamin C Baseline Final 96.5±65.643.6±32.7 101.2±107.059.0±60.1 135.1±96.566.1±65.7 146.0±103.278.0±67.9 129.1±204.968.3±61.3 121.3±100.1267.7±208.7 Vitamin D Baseline Final 4.7±3.91.7±2.0 1.8±2.42.7±3.5 2.2±2.02.5±2.6 8.5±3.01.1±1.4 2.7±3.11.8±2.1 1.0±0.24.3±0.9 Vitamin E Baseline Final 13.3±7.17.5±3.8 8.7±5.99.2±7.5 9.4±4.18.2±6.4 20.7±13.05.6±2.0 9.0±5.77.9±4.7 7.1±4.319.4±13.8 Vitamin B6 Baseline Final 1.4±0.60.9±0.2 1.3±0.61.0±0.6 1.1±0.41.3±0.9 1.7±1.01.2±0.3 1.5±0.61.0±0.6 1.6±1.01.1±0.07 Folic Acid Baseline Final 214.9±69.4180.8±131.6 164.4±105.9163.1±100.7 208.0±121.1160.3±100.8 176.0±36.892.0±1.4 163.1±73.4152.4±73.2 189.7±160.2214.0±13.5

2.6 Dietary intake

Table 8 presents the average nutrient intake of the compliant and non-compliant subjects in the 3 groups. These intakes are the baseline and final values for the protocol as determined using the 24-hour recall method. Table 8 shows that Group 1 reported a reduction in final uptake of 2174 kJ, Group 2 by 2505 kJ, and Group 3 by 1515 kJ compared to baseline. Table 8 also shows that these decreases in energy intake were mainly due to lower fat and added sugar intake.

Table 9 : Serum liposomes (mmol/L) of compliant and non-compliant persons in each group variable First group Second Group The third group C NC C NC C NC number of objects 14 10 twenty three 2 twenty two 4 Total cholesterol: baseline SD 5.03±1.22 5.47±1.38 5.32±0.80 5.45±1.61 5.41±1.26 5.81±0.93 Total Cholesterol: Final SD 4.96±0.93 5.23±0.98 4.95±0.76 6.21±0.76 5.26±2.61 5.61±0.77 Changes in total cholesterol 0.07 0.24 0.37 0.76↑ 0.15 0.20 LDL-C baselineSD 3.48±0.89 3.75±1.39 3.63±0.74 3.45±1.15 3.62±0.99 3.77±0.82 LDL-C final SD 3.24±0.54 3.54±0.92 3.36±0.58 4.25±1.86 3.47±1.00 3.59±0.50 Changes in LDL-C 0.24 0.21 0.27 0.80↑ 0.15 0.18 HDL-C Baseline SD 1.17±0.42 1.28±0.31 1.25±0.36 1.07±0.61 1.25±0.27 1.39±0.20 HDL-C Final SD 1.11±0.33 1.28±0.32 1.17±0.33 1.14±0.35 1.23±0.28 1.33±0.12 Changes in HDL-C 0.06 0.00 0.08 0.07↑ 0.02 0.06 TC HDL-C % Baseline SD 23.9±8.8 24.7±8.5 23.7±7.6 19.7±1.3 24.7±9.2 24.3±3.7 TC HDL-C% Final SD 22.5±5.1 25.2±7.0 23.7±6.4 18.8±2.2 24.9±8.2 23.8±1.1 Changes in HDL-C 1.4 0.5↑ 00.0 0.9 0.2↑ 0.5 Triglyceride baseline SD 1.19±0.68 0.99±0.57 0.98±0.38 2.08±0.47 1.22±0.92 1.43±0.45 Triglyceride Final SD 1.68±1.29 0.91±0.44 0.92±0.36 1.82±0.88 1.23±1.03 1.53±0.20 Changes in Triglycerides 0.49↑ 0.08 0.06 0.26 0.01↑ 0.10↑

LDL-C = low-density lipoprotein cholesterol

HDL-C = high-density lipoprotein cholesterol

C = Compliant (see below)

NC = Non-Conforming (see below)

BMI = body mass index

SD = standard deviation

a, b, c... with the same sign are significantly different (p≤0.05):

Within-group, paired-sample test for variation between groups, Kruskal-Wallis test (nonparametric)

Group 1: anorexic composition + meal

Group 2: placebo + meal

Group 3: Micronutrient Mix + Meal

3 Discussion

3.1 Compliant and non-compliant

The primary objective of this study was to evaluate the effect of two treatments (two potential weight loss agents, preparations, supplements or products) on obese subjects receiving a calorie-restricted diet compared to a placebo group receiving diet + inactive placebo. Effects on weight loss. Measuring dietary adherence is always difficult in such studies. However, since the effect of two specific products was measured, it was decided to measure compliance with the given product (as well as the placebo product) during individual weekly interviews when subjects were weighed and at the end of the 12 week study. This distinction between "compliant" and "non-compliant" should not be confused with "responders and non-responders". In the latter case, subjects who comply with treatment but do not show expected results are often described as "non-responders".

Since the reported compliance with the product was used rather than the outcome (i.e. weight loss) as the criterion for distinguishing between the compliant and the non-compliant, the two subgroups in each group were compared and the compliance of the 3 groups was compared Can effectively evaluate the effect of different products. However, the group that did not comply with the product also lost some weight (1.6, 2.3 and 2.8 kg, respectively), suggesting that these subjects accepted the calorie-restricted diet to some extent. The weight loss in Group 2 also indicated that dietary compliance was acceptable to some extent. This suggests that those who do not comply with these products may have problems complying with the diet. Levels of motivation to lose weight may vary among these subjects.

Adherence to a calorie-restricted diet in obese subjects is a problem, and underestimation of energy intake in obese individuals is an accepted phenomenon (7). The use of reported dietary intake as a measure of compliance is therefore problematic. Regardless, the reported dietary intake of these subjects at baseline and at the end of the study is shown in Appendix 4. Reported dietary intakes were those of the previous day, and not customary intakes (as measurable by food frequency questionnaires). Since obese subjects are known to underestimate, the risk of underestimation can be reduced during the 24-h recall period.

Group 2 reported the greatest mean energy deficit and Group 3 the smallest. The difference was significant compared to group 1, which reported no greater energy deficit despite the greatest weight loss. This suggests that the anorexic composition may also have an effect on energy expenditure (not only intake). However, this study was not designed to determine the mechanism.

3.2 Weight Loss

The results shown in Table 5 demonstrate that Group 1 subjects lost more significant weight than Group 2 subjects, and their BMI decreased more significantly than Group 2 and Group 3 submissives.

Over a period of 12 weeks (84 days), Groups 2 and 3 compliant subjects lost an average of 5.8 and 5.5 kg, indicating that these subjects achieved energy deficits of approximately 220,400 and 209,000 kilojoules during this period. This translates into a daily energy deficit of between 2488-2624 kilojoules. Group 1 subjects lost an additional 3.4 kg, representing an additional energy deficit of 129,200 kJ over 12 weeks or an energy deficit of 1538 kJ per day. Overall, Group 1 subjects achieved an average daily deficit of 4162 kJ.

As already mentioned in 5.1, the question that needs to be answered is whether the "additional" effect on weight loss induced by the anorexic composition is the result of reduced intake due to appetite suppression (better compliance with the calorie-restricted diet) ), or does the anorexic composition have an independent effect on metabolism? Calcium, a substance in anorexic compositions, has been reported to act as an anorexic at high doses (8). Whether the additional amount of calcium (1265 mg/day) provided by the anorexic composition will suppress appetite has not been determined. Regardless, it seems prudent to recommend that subjects taking micronutrient blends receive a low-calcium diet.

3.3 body circumference

Body circumference (Table 6) was significantly reduced in the submissives in all 3 groups. If the waist:hip ratio is calculated using the mean of waist and hip, it appears that the reduction in waist circumference is slightly greater than the reduction in hip circumference. The result was a slightly lower waist:hip ratio in groups 1, 2, and 3, 0.032, 0.007, and 0.015, respectively. The waist:hip ratio can be used to distinguish male or upper body obesity from female or lower body obesity (1). A value ≥1.0 in males and ≥0.85 in females is referred to as androgenic obesity (1). All three groups had baseline values > 0.800. The larger reduction in group 1 (from 0.838 to 0.806) may be due to the larger weight loss.

4 Conclusion

4.3 Main Findings

Therefore, the main finding of this study is that subjects taking the anorexic composition twice daily for 12 weeks lost significantly more weight and had a significantly lower BMI than subjects regularly taking placebo or the micronutrient mixture. Furthermore, the anorexic composition is further made feasible and industrially usable by presenting the calcium acetate in a form suitable for oral administration, such as a liquid drink.

4.4 Conclusion

From these results it can be concluded that the anorexic composition is an effective weight loss agent that will help subjects on a calorie restricted diet to lose greater weight. The anorexic composition did result in further weight loss since this effect was not observed in the group without the anorexic composition but only the micronutrient mix itself.

4.5 recommended

The anorexic composition can therefore be recommended as an effective weight loss supplement that will help obese subjects receiving a calorie restricted diet achieve greater weight loss than the diet alone. By presenting calcium acetate in a drinkable and palatable product, by masking its malodorous taste, the present invention provides an industrially usable and virtually acceptable product.

Applicants therefore foresee that the anorectic compositions and methods of treating obesity of the present invention are an effective method for reducing body weight.

It will be apparent that various changes may be made in the anorectic composition and use thereof according to the invention without departing from the scope of the appended claims.

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Claims (15)

CLAIMS 1. An anorexic composition comprising calcium acetate in a form suitable for oral administration and absorption in the stomach and small intestine. 2. An anorexic composition according to claim 1, comprising a flavoring agent to mask the malodorous taste of calcium acetate, thereby rendering the composition suitable for oral administration and absorption in the stomach and small intestine. 3. The anorectic composition according to claim 1 or claim 2, wherein calcium acetate accounts for 54%-89.9% based on the mass of the anorectic composition. 4. The anorectic composition according to claim 2, wherein the flavoring agent accounts for 5%-20% based on the mass of the anorectic composition. 5. An anorectic composition as claimed in any one of the preceding claims comprising a sweetener. 6. The anorectic composition as claimed in claim 5, wherein the sweetener accounts for 5%-25% based on the mass of the anorectic composition. 7. An anorexic composition according to any one of the preceding claims comprising pectin. 8. The anorectic composition according to claim 7, based on the mass of the anorectic composition, pectin accounts for 0.1%-1%. 9. An anorexic composition according to any one of the preceding claims, in the form of a water soluble powder. 10. A method of treating obesity comprising the step of: administering the anorexic composition according to any one of claims 1-9 and 14 to a human in need thereof. 11. The method of claim 10, wherein the anorexic composition is administered in the form of a drink or food. 12. A method as claimed in claim 10 or 11, comprising the step of administering to said person in need thereof at least twice daily an amount of the anorexic composition sufficient to administer an effective amount of 3g to 7g of calcium acetate to the person. 13. The method of claim 12, wherein an effective amount of 5 g of calcium acetate is administered to said human twice daily. 14. An anorectic composition substantially as herein described and exemplified. 15. A method of treating obesity substantially as herein described and exemplified.