METHOD OF REDUCING WEIGHT REGAIN IN MAMMALS

Abstract

Method of reducing weight regain in mammals after a hypocaloric weight-loss diet. A quinoa extract without saponins are used.

Claims

1. A method of reducing weight regain in mammals after a hypocaloric weight-loss diet using phytoecdysones.

2. The method according to claim 1, further comprising stabilizing a diameter of adipocytes after the hypocaloric weight-loss diet.

3. The method according to claim 1, further comprising stabilizing an insulin sensitivity previously improved by the hypocaloric weight-loss diet.

4. The method according to claim 1, further comprising the step of selecting the phytoecdysones from 20-hydroxyecdysone, makisterone A, 24-epimakisterone A, 24(28)-dehydromakisterone A, 20,26-dihydroxyecdysone, and combinations of two or more of these components.

5. The method according to claim 1, further comprising the step of providing the phytoecdysones in a form of a plant extract.

6. The method according to claim 5, wherein the plant extract comprises at least 1% phytoecdysones by weight.

7. The method according to claim 5, wherein the plant extract is from quinoa.

8. The method according to claim 1, further comprising the step of incorporating the phytoecdysones into a composition that can be orally administered.

9. A method of reducing weight gain according to claim 1 using a quinoa extract without saponins, enriched with one or more phytoecdysones, the quinoa extract prepared as follows: separating flour from bran of quinoa seeds; water extraction of the bran of the quinoa seeds to provide an aqueous extract; solid/liquid separation and centrifugation of the aqueous extract; heating of supernatant to precipitate proteins; and purification by chromatography of the supernatant to enrich it with phytoecdysones and to eliminate saponins from the quinoa extract.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0031] FIGS. 1A, 1B: Graphs representing the weight change in obese individuals on a hypocaloric diet;

[0032] FIGS. 2A, 2B: Graphs representing the change in adipocyte diameter in obese individuals on a hypocaloric diet;

[0033] FIGS. 3A, 3B: Graphs representing the change in insulin levels in obese individuals on a hypocaloric diet;

[0034] FIGS. 4A, 4B: Graphs representing the change in insulin sensitivity in obese individuals on a hypocaloric diet;

[0035] FIG. 5: The chemical formulas of phytoecdysones present in a composition according to an embodiment of the invention.

DETAILED DESCRIPTION OF THE EMBODIMENTS

[0036] In the invention, it is proposed to provide a dose of phytoecdysones in the form of purified molecules, or by means of a plant extract enriched with phytoecdysones, so as to prevent weight regain, known as the rebound effect, in obese mammals on a hypocaloric weight-loss diet.

[0037] According to the invention, it is possible to provide said dose of phytoecdysones in the form of a plant extract, such as quinoa, incorporated for example in food added to an individual's daily diet. One gram of quinoa that has been enriched with up to 2% phytoecdysones by weight contains 20 milligrams of phytoecdysones. To obtain the same quantity of phytoecdysones from quinoa seeds, it would be necessary to consume 50 grams of unprocessed quinoa seeds (Dini et al., 2005; Kumpun et al., 2011). The quinoa extract according to the invention may also contain up to 50 times more phytoecdysones than the quinoa seeds from which it is produced.

I. An Example of a Method for Preparing the Quinoa Extract Enriched with Phytoecdysones (Extract A)

[0038] The quinoa seeds are first ground to separate the flour from the bran of the seed. An extraction is then carried out by adding 4,000 L to 400 kg of bran. The aqueous extract undergoes solid/liquid separation, followed by centrifugation. The resulting supernatant is subjected to 90 C. heat to precipitate the proteins. The aqueous extract is then purified by being passed through a column of food resin for the purpose of enriching it with phytoecdysones. The ethanol eluate is then dried by means of spray drying after adding a bit of maltodextrin, appropriated to adjust the 20.2% content in weight of 20-hydroyecdysone (20E).

[0039] Such a sequential extraction makes it possible to eliminate saponins from the extract, which are abundant in quinoa seeds (Muir et al., 2002) and which would create a bitter taste in said extract, and most sugars.

[0040] The obtained extract contains a blend of phytoecdysones, of which 85-90% is 20-hydroxyecdysone. The remainder is comprised of other very similar phytoecdysones, such as makisterone A, 24-epimakisterone A, 24(28)-dehydromakisterone A, 20,26-dicydroxyecdysone (Kumpun et al, 2011). The structures of these components are shown in FIG. 5.

[0041] An extract similar to extract A, usable as part of the invention, is notably sold under the number QUINOLIA, a registered US Trademark owned by one of the applicant (Biophytis SA).

II. A Double-Blind Clinical Trial on the Effects of Extract A on Obese Individuals on a Hypocaloric Diet for Six Weeks Followed by a Stabilization Diet for Six Weeks Protocol

[0042] The effect of extract A was studied as part of a double-blind clinical trial on 60 overweight and obese volunteers, comprised of 18 men and 42 women with a BMI ranging from 27 to 38. The volunteers were given a hypocaloric diet of 1200 kcal for women and 1500 kcal for men for six weeks. The hypocaloric diet is followed by a six-week stabilization diet, with 20% more calories than the hypocaloric diet. Parameters such as insulin levels, weight change, adipocyte diameter, and muscle strength were measured during the visits at the start and end of the hypocaloric and stabilization phases.

[0043] Subjects were split into two groups. A first group (extract A group) received six capsules of extract A, containing a total of 40 mg of phytoecdysones, in three daily doses, throughout the duration of the test.

[0044] A second control group (placebo group) received six capsules of placebo in three daily doses, for the same duration.

[0045] Measurements were taken at the beginning of treatment (W0), at the end of the sixth week of the diet (W6), and at the end of the twelfth week of the diet (W12).

Measurement of Weight Change During the Weight-Loss and Stabilization Diets

[0046] The effect of extract A during a hypocaloric diet was studied based on weight change (FIGS. 1A and 1B).

[0047] The placebo and extract A groups showed respective weight losses of 4.05 kg and 3.86 kg during the first phase of the diet, called the weight-loss phase.

[0048] During the second phase of the diet, called the stabilization phase, the extract A group continued to lose weight (0.483 kg), while the placebo group posted an average gain of +0.504 kg.

[0049] The study of relative weight change in the tested individuals shows that, in the extract A group, only 10% of individuals rebounded (a gain of 0.05 to 0.1 kg/day), compared to 28% of the placebo group.

[0050] The same extract A group had 20% of individuals who had lost 0.06 to 0.15 kg/day, while in the placebo group, only 10% of individuals fell into that category.

Measurement of Adipocyte Diameter During the Weight-Loss and Stabilization Diets

[0051] The effect of extract A during a hypocaloric diet was studied based on adipocyte diameter change (FIGS. 2A and 2B).

[0052] During the weight-loss phase, the average adipocyte diameter was reduced both in the extract A group (10.94 m) and in the placebo group (8.80 m).

[0053] During the stabilization phase, the average diameter continued to decline, with a significant difference between the extract A group (9.25 m) and the placebo group (5.99 m) group.

[0054] This result is combined with a greater loss in body fat during the stabilization phase in the extract A group. In fact, the loss of body fat during the stabilization phase was 0.74 kg for the extract A group, but only 0.33 kg for the placebo group.

Measurement of Insulin Levels and Insulin Resistance During the Weight-Loss and Stabilization Diets

[0055] The effect of extract A during a hypocaloric diet was studied based on the change in insulin levels (FIGS. 3A and 3B) and insulin resistance (FIGS. 4A and 4B). The HOMA-IR (Homeostasis Model Assessment of Insulin Resistance, FIGS. 4A and 4B) index is a marker of insulin resistance.

[0056] Blood insulin levels declined during the weight-loss phase in the extract A group (18.90 pmol/L) and the placebo group (12.60 pmol/L). They climbed back up during the stabilization phase in the placebo group (7.69 pmol/L), but they stabilized in the extract A group. The treatment with extract A makes it possible to stability blood insulin levels in the stabilization phase and to decrease them significantly more than placebo throughout treatment.

[0057] Insulin resistance, measured with the HOMA-IR index, declined in both groups during the weight-loss phase. It remained constant in the extract A group during the stabilization phase, but it went back up significantly in the placebo group.

Conclusions

[0058] The administration of extract A makes it possible for object subjects to avoid weight regain during the second phase, called the stabilization phase, of the hypocaloric weight-loss diet.

[0059] Furthermore, the administration of extract A allows for a more significant decline in body fat and average adipocyte diameter during the stabilization phase. The administration of extract A finally makes it possible to lower insulin levels and maintain the improved insulin sensitivity brought about by the hypocaloric diet during this same phase.

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