Patent Application
20200222451
The invention relates to compositions and formulations for use in increasing gastrointestinal microbiota diversity. Such compositions are particularly useful in sustaining and/or managing weight loss over a prolonged period of time.
Overweight and obese are conditions defined as abnormal or excessive fat accumulation that may impair health. It results from imbalances in the body's regulation of energy intake, expenditure and storage.
Obesity is one of the greatest public health challenges of the 21st century. It is a complex condition, one with serious social and psychological dimensions, that affects virtually all age and socioeconomic groups in both developed and developing countries. The health consequences of obesity range from increased risk of premature death to serious chronic conditions that reduce the overall quality of life. Excess weight is the fifth leading risk for global deaths. At least 2.8 million adults die each year as a result of being overweight or obese. In addition, 44% of the diabetes burden, 23% of the ischaemic heart disease burden and between 7% and 41% of certain cancer burdens are attributable to being overweight or obese.
Among the reasons that have led to the dramatic increase in obesity are an increase in the intake of high fat, salt and refined sugar foods that are energy rich but otherwise low in nutritional value (vitamins, minerals, micronutrients) in combination with an increasingly sedentary nature to everyday life with a dramatic decrease in physical activity.
Prebiotics have attracted interests as candidate compounds for the control of obesity and associated metabolic disorders. In animal studies, prebiotics have been shown to regulate the intake of food, prevent weight gain, beneficially alter lipid metabolism and reduce obesity-related inflammation. So far, most studies have focused on simply supplementing the diet with inulin and fructooligosaccharides (FOS).
WO2015/067936 discloses compositions for weight management comprising: a) a microbiome modifying component; b) a satiety modifying component; and c) a metabolic modifying component.
Griffin et. al., (2017) Cell Host & Microbe, 21, 1-13, January 11, discloses how dietary practices can alter bacterial diversity in the human gut microbiota and that dispersal of diet-responsive bacterial taxa can enhance subsequent responses to diet interventions.
It is an object of the present invention to provide a formulation which can be used for increasing gastrointestinal microbiota diversity. It would be beneficial if the formulation provided could be used for weight management—whether as a food supplement, additive or potential treatment. It is a further object of the present invention to provide a formulation which can reduce or modulate weight gain—especially for modulating and maintaining weight loss over a prolonged period of time. It would also be preferable that the formulation could be easily administered as either a medicament or a food supplement or a calorie restricted meal replacement product.
In accordance with a first aspect of the present invention, there is provided a composition for use in increasing gastrointestinal microbiota diversity comprising:
a) glucomannan;
b) chromium; and
c) a prebiotic.
The term “chromium” covers all dietary chromium salts, including trivalent chromium (Cr(III) or Cr3+) which naturally occurs in trace amounts in foods and waters. Preferably, the chromium salt comprises chromium picolinate.
The term “prebiotic” is intended to mean a selectively fermented ingredient that allows specific changes, both in the composition and/or activity in the gastrointestinal microflora flora that confers benefits upon host wellbeing and health.
Preferably the prebiotic comprises one or more selected from: inulin, fructooligosaccharides (FOS), galactooligosaccharides (GOS), α-gluco-oligosaccharides and β-glucans and combinations thereof. More preferably, the prebiotic comprises fructans including fructo-oligosaccharides (FOS) and inulin and combinations of fructo-oligosaccharides and inulin. Most preferably, the prebiotic comprises fructans having a high oligofructose content of up to 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95%. The composition may comprise glucomannan in the range of about 0.6 g to about 1.4 g; chromium in the range of about 60 μg to about 100 μg; and/or prebiotic in the range of about 1.5 g to about 4.0 g. More preferably, the composition may comprise glucomannan in the range of about 0.8 g to about 1.2 g; chromium in the range of about 70 μg to about 90 μg; and/or prebiotic in the range of about 0.5 g to about 2.5 g. Even more preferably, the composition comprises glucomannan present at about 1 g; chromium present at about 79 μg; and/or prebiotic present in the range of about 1 g to about 2 g.
The glucomannan may be agglomerated with other components such as with a carrier such as maltodextrin or dextran to improve dispersion, increase solubility and enhance the satiety effect.
The composition may be formulated in a number of ways, but it is preferred that it is in the form of a food stuff or food additive, a dietary supplement (i.e. the composition could be blended with foods/drinks or consumed alongside foods/drinks), or a meal replacement drink or snack bar.
The composition may be for use in increasing gastrointestinal microbiota diversity over a prolonged period of time. That is to say that it increases gastrointestinal microbiota diversity by up to 1 week, 1 month, 3 months or more. It has been surprisingly identified by the present inventors that increasing gastrointestinal microbiota diversity over a prolonged period of time can assist with individuals reducing their weight and, more importantly, maintaining their lower weight over the longer term.
It will be apparent to the skilled addressee that the composition may also be in any easily administered form, for example in the form of a powder, tablet, or capsule. The composition may further comprise an excipient or carrier compound to modify the release profile of one or more of the components through the intestinal environment.
The composition may further comprise one or more active ingredients selected from: vitamins, minerals, phytochemicals, antioxidants, and combinations thereof.
Vitamins may include fat soluble vitamins such as vitamin A, vitamin D, vitamin E, and vitamin and combinations thereof. In some embodiments, vitamins can include water soluble vitamins such as vitamin C (ascorbic acid), the B vitamins (thiamine or B1, riboflavoin or B25 niacin or B3, pyridoxine or B6, folic acid or B9, cyanocobalimin or B12, pantothenic acid, biotin), and combinations thereof.
Minerals may include, but are not limited to, sodium, magnesium, chromium, iodine, iron, manganese, calcium, copper, fluoride, potassium, phosphorous, molybdenum, selenium, zinc, and combinations thereof.
Antioxidants may include but are not limited to ascorbic acid, citric acid, rosemary oil, vitamin A, vitamin E, vitamin E phosphate, tocopherols, di-alpha-tocopheryl phosphate, tocotrienols, alpha lipoic acid, dihydrolipoic acid, xanthophylls, beta cryptoxanthin, lycopene, lutein, zeaxanthin, astaxanthin, beta-carotene, carotenes, mixed carotenoids, polyphenols, fiavonoids, and combinations thereof.
Phytochemicals may include but are not limited to cartotenoids, chlorophyll, chlorophyllin, fiber, flavanoids, anthocyamns, cyaniding, delphinidin, malvidin, pelargonidin, peonidin, petunidin, flavanols, catechin, epicatechin, epigallocatechin, epigailocatechingallate, theaflavins, thearubigins, proanthocyanins, flavonols, quercetin, kaempferol, myricetin, isorhamnetin, flavononeshesperetin, naringenin, eriodictyol, tangeretin, flavones, apigenin, luteolin, lignans, phytoestrogens, resveratrol, isoflavones, daidzein, genistein, glycitein, soy isoflavones, and combinations thereof.
In accordance with another (but related) aspect of the present invention, there is provided a functional foodstuff for use in increasing gastrointestinal microbiota diversity comprising:
a) glucomannan;
b) chromium; and
c) a prebiotic.
The prebiotic preferably comprises fructooligosaccharides (FOS) and inulin and combinations of fructooligosaccharides (FOS) and inulin.
Preferably, the foodstuff comprises glucomannan in the range of about 0.6 g to about 1.4 g; chromium in the range of about 60 μg to about 100 μg; and/or prebiotic in the range of about 1.0 g to about 4.0 g. More preferably, the foodstuff comprises glucomannan in the range of about 0.8 g to about 1.2 g; chromium in the range of about 70 μg to about 90 μg; and/or prebiotic in the range of about 1.0 g to about 2.5 g. Most preferably, the foodstuff comprises glucomannan present at about 1 g; chromium present at about 79 μg; and/or prebiotic present in the range of about 1 to about 2 g.
The foodstuff may be in the form of as a dietary supplement, a meal replacement drink or snack bar. If the foodstuff is in the form or a meal replacement drink or snack bar, it may be formulated with one or more of the following ingredients: whey, skimmed milk powder, oat flour, MCT powder, soya or sunflower lecithin, flaxseed, chia seed, xanthan gum, flavourings, natural and/or artificial sweeteners (for example Stevia), vitamins and minerals, superfoods and extracts thereof, natural and/or artificial flavourings and/or colorants and probiotics
The foodstuff may be for use in increasing gastrointestinal microbiota diversity over a prolonged period of time.
The foodstuff may further comprise active ingredients selected from: vitamins, minerals, phytochemicals, antioxidants, and combinations thereof.
The composition as herein above described and/or foodstuff as hereinabove described, may be taken up to three or four times a day as part of a calorie controlled diet regime. The composition or foodstuff may be taken during and/or after a reduced calorie intake diet regime. Such a calorie controlled diet regime may comprise consuming up to four products over the course of the day in order to replace two out of three daily meals. The four products may be in the form of two meal replacement drinks and two mid-meal snack bars. The two meal replacement drinks may include two thirds of the daily amount, whereas the two mid-meal snack bars would collectively include one third of the daily amount.
The composition or foodstuff may comprise glucomannan in a daily dose in the range of about 1.8 g to about 4.2 g; chromium in a daily dose in the range of about 180 μg to about 300 μg; and/or prebiotic in a daily dose in the range of about 1.0 g to about 12 g.
The composition or foodstuff may comprise glucomannan in a daily dose in the range of about 2.4 g to about 3.6 g; chromium in a daily dose in the range of about 210 μg to about 270 μg; and/or prebiotic in a daily dose the range of about 1.5 g to about 12 g.
The composition or foodstuff comprises glucomannan in a daily dose of about 3 g; chromium in a daily dose of about 79 μg; and/or prebiotic in a daily dose in the range of about 2.0 g to 12 g.
In accordance with another aspect of the present invention, there is provided a method of promoting or maintaining weight loss in an individual, the method comprising administering the composition of foodstuff as herein above described. The composition or foodstuff may be administered up to 3 times a day. Preferably, the composition or foodstuff is administered before, during (or as part of) or after a reduced calorie intake diet regime.
In accordance with another aspect of the present invention, there is provided a use of a composition as herein above, in the manufacture of a medicament for the treatment of obesity.
Embodiments of the present invention will now be described, by way of example only with reference to the following figures and examples detailed below.
A ‘SlimBiome’ formulation including the following components was prepared in accordance with Table 1 and placed in a sachet.
The glucomannan component is marketed under Glucomannan 90% (E-425i) and sourced from Cambridge Commodities Limited, 203 Lancaster Way Business Park, Ely, Cambridgeshire, CB6 3NX, UK.
CHROMAX® is the chromium component and sourced from Ingredia Nutritional S. A., 51, Avenue Fernand Lobeddez, CS, 60946, 62033 Arras Cedex, France and has a specification of 12 - 12.5% of chromium. CHROMAX® is salt of chromium and picolinic acid in powder, with a standardized content of 12-12.5% pure chromium. Picolinic acid is a natural tryptophan metabolite making it highly bioavailable.
The FOS Beneo P95 component was sourced from BENEO GmbH Maximilianstrasse 10, 68165 Mannheim, Germany. The oligofructose (fructo-oligosaccharide, FOS) are composed of fructose units linked by a beta-1,2-bond, partly with an end-standing glucose unit. The degree of polymerisation (=number of monosaccharide units) ranges between 2 and 8 and is formed by partial enzymatic hydrolysis of chicory inulin. It has an oligofructose content of 95% and a sweetness level of 30% and is a powder form.
A placebo formulation was also prepared without the active ingredients of glucomannan, chromium and FOS, and the components shown in Table 2 below, and this formulation inserted into a sachet.
The contents of the sachets were then blended with other ingredients to produce calorie restricted powdered meal replacement shake or a meal replacement snack bar.
For the powdered meal replacement shake or snack bar, the sachet was blended with the following ingredients: whey, skimmed milk powder, oat flour, MCT powder, soya or sunflower lecithin, flaxseed, chia seed, xanthan gum, flavourings, natural and/or artificial sweeteners (for example Stevia), vitamins and minerals, superfoods and extracts thereof, natural and/or artificial flavourings and/or colorants and probiotics. Other ingredients which are specific to the meal replacement may be included, such as vanilla pods or raw or processed cocoa.
A customer survey was commissioned in order to gain feedback from customers who had bought calorie restricted meal replacement products including the SlimBiome® formulation. The specific objectives of the survey were to understand the effectiveness of the meal replacements, the likability of the products & flavours and the appeal of specific ingredients.
The customer survey was conducted between July and August 2016. 127 customers were contacted who had bought the product directly. The only recruitment criteria set was the customers had purchase of the product directly via the official sales website and as such the respondents were free living adults, with no specified weight range, health status or dietary restriction, so as to replicate a human intervention study.
The survey was conducted in two phases: phase 1-27th July 2016—87 contacted; and phase 2—18th August 2016—40 contacted. Personal information collected was limited to age and gender. No details were obtained on the respondents as to existing physical health condition, eating or exercise habits.
Overall, response to the calorie restricted meal replacement range was positive with the majority of respondents losing weight during the period they had been using the products and liking the taste of the products and finding the active ingredients as a motivating benefit. Verbatim comments suggest that respondents were open to more flavours and formats in the range, but many had managed to stick with the calorie restricted meal replacement range plan unlike other plans. Some respondents stated that they enjoyed the diet which wasn't normal for them as they had previously not stuck to diets, whilst others mentioned that they were never hungry.
Effectiveness of the calorie restricted meal replacement range
100% of those on the plan for more than 1 week stated that they had lost weight. For the 53% of respondents who had been on the plan for 3 weeks or more, the median weight loss was 7-9 lbs (3.175-4.082 kgs) in total. On average, the longer the respondents were on the plan the greater weight loss recorded (i.e. those on the plan for 3 weeks lost more on average than those on the plan for 2 weeks). Respondents were only asked to record their total weight loss at the time the survey was conducted).
83% of respondents agreed with the statement that “I do feel less hungry than before”, 100% of respondents claim that “I am eating less overall”, 97% of respondents claim that “I snack less”.
The addition of Slimbiome® formulation “really appealed” to respondents.
With reference to
With reference to
In respect of
With reference to
With reference to
With reference to
With reference to
With reference to
The study was carried out to determine the effect of SlimBiome® formulation on satiation (fullness), satiety (hunger/cravings between meals) and food intake/choice. Product tolerance (and side-effects), cognitive ability (in the form of mood/cravings) and the ease of following a following a meal plan/compliance with the meal replacement products incorporating the Slim Biome® formulation was also assessed.
The study was conducted on 40 female subjects aged 21 to 65 years, with a BMI >27.5-32.5 kg/m2. The study was in the form of a prospective, randomized, parallel-group trial with two groups: Dietetic advice plus placebo (control) or Dietetic advice plus SlimBiome three times a day (test).
To be included in the study, the subjects had to also fulfil the criteria that they: had not followed a calorie restricted diet within the last month and had not lost a significant amount of weight in the previous year; had not increased physical activity levels in the past 2-4 weeks or intending to modify them during the study; were willing, able and likely to comply with all study procedures and restriction including being willing to follow the calorie restricted diet; and were able to eat most everyday foods. Subjects were excluded on the following grounds that they: had significant health problems; were taking medication or supplements known to affect appetite or weight within the past month and/or during the study; were pregnant, planning to become pregnant or breastfeeding; had a history of anaphylaxis to food; had known allergies or intolerance to foods and/or to the study materials (or closely related compounds) or any of their stated ingredients; had a BMI <27.5 kg/m2 or >32.5 kg/m2; had reported that they were currently undergoing a calorie restricted diet or having lost significant amount of weight in the previous year; had abnormal eating behaviour; were smokers and those who have recently ceased smoking; had participation in another experimental study or receipt of an investigational drug/product within 30 days of the screening visit; had significantly changed their physical activity in the past 2-4 weeks or who intend to change them during the study; were receiving systemic or local treatment likely to interfere with the evaluation of the study parameters; were on specific food avoidance diets; and had worked in appetite or feeding related areas.
All participants followed standard dietetic advice supplement and also had access to additional on-line material. They were advised on product storage and use conditions prior to use to ensure product consistency throughout the period of the study. The participants were instructed to take their respective products (containing either the placebo or Slimbiome® formulation) daily with water before each of the three main meals.
The following parameters were assessed during the study visit: anthropometric measurements; mood (PANAS) and craving (COEQ) measures; attentional bias (visual probe task); food choice (LFCT); food responsiveness (PoF); wellbeing (PSS and BDI); experience of programme; and experience of appetite.
Each participant attended a total of 3 study visits (plus screening). Assessments took take place at T=0, 1, and 4 weeks and the following measurements taken:
Example meal replacement snack bar and dehydrated shake formulations were formulated as follows:
As part of a calorie controlled diet regime, an individual would look to consume up to four products over the course of the day in order to replace two out of three daily meals. The four products may be in the form of two meal replacement drinks and two mid-meal snack bars according to the formulas outlined in Tables 3 and 4 above. It will be obvious to the skilled addressee that the formulas may be altered so as to enable the production of differently tasting products, which still have the beneficial effect of increasing the gastrointestinal microbiota diversity and ultimately facilitating weight loss.
Meal replacement snack bar and shake formulations Meal replacement snack bar and dehydrated shake formulations were produced on the basis of the following composition as defined below in Table 5.
A 201 calorie healthy meal replacement vanilla bean shake was formulated with the following ingredients: MCT (medium-chain triglycerides fats) Powder, Skimmed Milk, Gluten Free Oat Flour, Soya Protein, Whey Protein (Milk), Maltodextrin, Natural Flavouring, Glucomannan Formula [Oligofructose, Glucomannan (Konjac root extract), Chromium Picolinate], Emulsifier (Soya Lecithin), Multivitamin Premix (vitamin A, Thiamin (B1), Riboflavin (B2), Niacin (B3), Pantothenic Acid (B5), vitamin B6, Folic Acid, Vitamin B12, Vitamin C, Vitamin D, Vitamin E, Biotin, Calcium, Phosphorus, Potassium, Iron, Zinc, Copper, Iodine, Selenium, Chromium, Manganese, Magnesium, Flaxseed, Chia (Salvia hispanica) Seeds, Greens Powder Premix (Broccoli, Spinach, Watercress, Green Kale, Barley Grass, Alfalfa, Coriander, Basil, Rosemary, Thyme, Yucca Root, Kelp, Avocado), Premix (Spirulina, Chlorella, Baobab fruit pulp, Maca), Thickener (Xanthan Gum), Live Probiotic Bacterial Cultures Complex (Lactobacillus Acidophilus, Bifidobacterium Bifidum), Sweetener (Steviol Glycosides). The shake was formulated with 1 g of glucomannan, 2 g of FOS and 0.083 g chromium.
The shake is intended promote healthy, sustainable weight loss with a marked increase in vitality which are made from real, wholefood ingredients and have all the healthy nutrients your body craves in one delicious tasting liquid meal.
The shakes are intended to be re-hydrated to the correct viscosity and two shakes consumed per day so as to replace two regular meals. Preferably, they are used to replace breakfast and dinner with a healthy meal shake. 1 sachet (40 g) of powder is blended or mixed with 250 ml to 350 ml of water and an additional glass of water or herbal tea taken.
A 115 calorie healthy peanut snack bar was formulated with the following ingredients: Chopped dates, gluten free oats (oats, oat bran 19.8%), air roasted peanuts (17.1%), sultanas, blanched peanuts (7.5%), sunflower seeds, vegetable glycerine, [Oligofructose, Glucomannan (Konjac root extract), Chromium Picolinate]. The bar was formulated with 0.5 g of glucomannan, 1 g of FOS and 0.041 g chromium.
An alternative bar is a 115 calorie healthy orange cacao snack bar was formulated with the following ingredients: Gluten free oats (oats, oat bran 25.1%), cashews, chopped dates, sultanas, vegetable glycerine, cacao nibs (4.3%), cacao powder (3.5%), cacao butter (3.5%), oligofructose (fibre), glucomannan (Konjac root extract), natural orange flavouring, chromium picolinate. The bar was formulated with 0.5 g of glucomannan, 1 g of FOS and 0.041 g chromium.
The bars are intended to be a healthy combination of cold pressed fruits, gluten free oats and seeds, with no added sugar, syrups or fillers. They can therefore be taken as a satisfying snack between meals, after exercising, on the way to work or as a delicious treat. Two bars are to be taken daily.
The forgoing embodiments are not intended to limit the scope of the protection afforded by the claims, but rather to describe examples of how the invention may be put into practice.
| Number | Date | Country | Kind |
|---|---|---|---|
| 1712151.8 | Jul 2017 | GB | national |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/GB2018/052147 | 7/27/2018 | WO | 00 |
