DIETARY REGIME FOR TREATMENT OF

ACNE AND OTHER INFLAMMATORY SKIN CONDITIONS

PRIORITY DOCUMENT

[00 1] The present application claims priority from United States Provisional Patent Application No. 61/895434 titled "DIETARY REGIME FOR TREATMENT OF ACNE AND OTHER

INFLAMMATORY SKIN CONDITIONS" and filed on 25 October 2013, the content of which is hereby incorporated by reference in its entirety.

TECHNICAL FIELD

[0002] The present invention relates to methods for controlling or preventing acne and other inflammatory skin conditions in humans.

BACKGROUND

[0003] Acne Vulgaris is the most common skin condition in the world, and while it is generally associated with adolescence for many people acne may arrive at an older age. or persist well into adulthood. Even a significant percentage of children (4-7 years) arc diagnosed with acne (1, 2).

[0004] Acne patients tend to be long-term consumers of over-the-counter (OTQ preparations, pharmaceuticals and prescribed medicines. Some patients with persistent acne have been reported to experience significant psychological injury related to the chronic and disfiguring nature of the condition (3).

[0005] For patients seeking professional help, clinical guidelines almost exclusively advise drug therapy. Research in the past thirty years has focused largely on pharmaceutical efficacy in the management of acne, achieved to varying effect with pharmacologically active compounds such as antibiotics, astringents, retinoids, herbal supplements and cleansers.

[0006] Unfortunately, many therapeutic interventions can cause serious adverse clinical events particularly in the case of oral retinoids. In addition, the overuse of topical medications, cleansers, or astringents can often worsen a patient's condition.

[0007] There is a need for new options to prevent or treat acne and other inflammatory skin conditions that resolve the significant disadvantages of existing treatments. SUMMARY

[0008] The present invention is predicated on the clinical finding that daily consumption of foods high in fructose, oligosaccharides and or polyol sugars can lead to acne or other inflammatory skin conditions. These clinical findings arc supported by the fact that acne has been rarely observed in societies that have maintained traditional diets. This effect has been noted in communities such as the Inuit of Canada (4, 5), Okinawa islanders of Japan (6), the Ache hunter gatherers of Indonesia, and the itavan Islanders of Papua New Guinea (6). The absence of acne in these populations clearly suggests die potential for underlying genetic or environmental factors, including diet.

[0009] In a first aspect, the present invention provides a method for assisting a subject to prevent or control an inflammatory skin disorder, the method comprising formulating a diet for the subject that is low in fructose, oligosaccharides and/or polyol sugars. f 0010] Embodiments of the first aspect of the invention may also comprise providing one or more food produces) in accordance with the formulated diet.

[001 1 ] In a second aspect, the present invention provides a method for assisting a subject to prevent or control an inflammatory skin disorder, the method comprising prescribing to the subject a diet that is low in fructose, oligosaccharides and or polyol sugars.

[0012] In a third aspect, the present invention provides a method for preventing or controlling an inflammatory skin disorder in a subject, the method comprising a<Jministcring to the subject a diet that is low in fructose, oligosaccharides and/or polyol sugars.

[0013] In a fourth aspect, the present invention provides a method for assisting a subject to prevent or control an inflammatory skin disorder, the method comprising: obtaining dietary information from the subject wherein said dietary information includes details of the subject's diet over a period of time; assessing the dietary information to deterrnine the total daily content of fructose, oligosaccharides and or polyol sugars in the subject's diet and or determining whether one or more foodstuffs in the subject's diet is high in fructose, oligosaccharides and or polyol sugars; and prescribing to the subject a diet that is low m fructose, oligosaccharides and/or polyol sugars.

[0014] In a fifth aspect, the present invention provides a method for selecting food products for a diet for preventing or controlling an inflammatory skin disorder, the method comprising: viewing a list of food products forming part of the diet; selecting one or more food product(s) from the list to form a daily diet list: calculating the total content of fructose, oligosaccharides and or polyol sugars contained in the foodstuffs on the daily diet list; providing feedback to the subject as to whether the foodstuffs on (he daily diet list contain a total amount of fructose, oligosaccharide.; and/or polyol sugars relative to a threshold daily value; and, if the amount of fructose, oligosaccharides and/or polyol sugars in the food produces) on the daily diet list is below the threshold daily value, creating a customised daily diet for the subject

[0015] In embodiments, (he method of the fifth aspect further includes ordering at least some of the food produces) in the customised daily diet for the subject. In embodiments, the ordering comprises communicating a food produces) order to a merchant remote from the communication device. In embodiments, the ordering also comprises ordering the food produces) from the food produces) order from a production and/or storage f cility and shipping the food produces) to the subject.

[001 ] Any one or more of the steps of the method of the fifth aspect may be implemented on a computer. For example, the list of food products forming part of the diet may be viewed on a display of a communication device, selection of the one or more food produces) from the list to form a dairy diet list may be carried out using a user interface of a communication device, and/or providing feedback to the subject may be carried using a user interface of a communication device.

[0017] In a sixth aspect, the present invention provides a database of information relating to the content of fructose, oUgosacchurides and or polyol sugars in a plurality of food products residing on a server computer, a user interface accessible by a subject and in communication with the database via a communication device, the user interface allowing the subject to select one or more food produces) from the database; a processor for calculating the total content of fructose, oligosaccharides and or polyol sugars in the selected one or more food product(s); and an output for displaying the total content of fructose, oligosaccharides and/or polyol sugars in the selected one or more food produces) to the subject.

[0018] In a seventh aspect, the present invention provides a packaged foodstuff wherein the packaging of the foodstuff contains information or refers to information regarding the diet referred to in any one of the first to sixth aspects.

[0019] In an eighth aspect, the present invention provides a foodstuff in conjunction with information relating to the diet referred to in any one of the first to sixth aspects.

[0020] In some embodiments of these aspects of the invention, the inflammatory skin disorder is acne vulgaris.

[0021 ] In some embodiments of these aspects of the invention, the inflammatory skin disorder is acne rosacea. (0022 j In some embodiments of these aspects of the invention, the inflammator skin disorder is general erythema.

[0023 J in some embodiments of these aspects of the invention, the inflammatory skin disorder is poikaderma de Civette.

[0024] in some embodiments of these aspects of (he invention, (he inflammatory skin disorder is eczema.

BRIEF DESCRIPTION OF THE FIGURES

10025] Embodiments of the present invention will be discussed with reference to the accompanying drawings wherein:

[0026] Figure 1 is a schematic diagram of a system for creating a customised daily diet in accordance with embodiments of the invention;

[0027] Figure 2 is a schematic diagram of a system for creating a customised daily diet implemented across a communications network in accordance with embodiments of the invention;

[0028] Figure 3 shows photographs of subject I at weeks 0, 2. 4 and 5;

10029] Figure 4 shows photographs of subject 2 at weeks 0, 2, 4 and 5;

[0030] Figure 5 shows photographs of subject 3 at weeks 0, 2, 4 and 5;

[0031 ] Figure 6 shows photographs of subject 4 at weeks 0, 2, 4 and 5;

[0032] Figure 7 shows photographs of subject 5 at weeks 0, 2 and 19;

[0033] Figure 8 shows photographs of subject 6 at weeks 0, 2, 4 and 1 ;

[0034] Figure 9 shows photographs of subject 7 al weeks 0 and 2;

[0035] Figure 10 shows photographs of subject 8 at weeks 0, 2 and 21 ;

[0036] Figure 11 shows photographs of subject 9 at weeks 0, 5 and 14;

[0037] Figure 12 shows photographs of subject 9 at weeks 0, 1, 2. 3, 5 and 14; and 10038] Figure 13 shows photographs of subject 1 1 at weeks 0 and 2. DETAILED DESCRIPTION

[0039] The present invention, and embodiments thereof, will now be described in more detail. For ease of description, reference will be made to die treatment or prevention of acne. However, this is for illustrative purposes only and it is intended that the embodiments and aspects described can also be used in the treatment or prevention of other inflammatory skin disorders.

[0040] Before proceeding it is important to note that various terms that will be used throughout the specification have meanings that will be well understood by a skilled addressee. However, for ease of reference some of these terms will now be denned.

[0041 ] As used herein, the term "a diet that is low in fructose, oligosaccharides and or polyol sugars" means a diet having a total content of fructose, oligosaccharides and/or polyol sugars thai is lower than the conventional or typical diet of the subject. In embodiments, the diet that is low in fructose, oligosaccharides and/or polyol sugars contains 40g or less per day of fructose, oligosaccharides and or polyol sugars. However, for some subjects (hat amount of 40g or less may not be low enough for the subject to prevent or control an inflammatory skin disorder. In those subjects, the individual tolerance limits in order to prevent or control an inflammatory skin disorder may need to be determined empirically. However, it is expected that the threshold level of 40g or less will be suitable for the majority of subjects.

[0042] As used herein, the term "oligosaccharide" means a saccharide containing typically three to ten sugar units. Examples of oligosaccharides commonly found in the diet include fructans and galadans. Fructo-oligosaccharides (FOS) arc found naturally in many vegetables, while inulin is a polysaccharide with a similar molecular structure to FOS but with a higher degree of polymerization.

[0043] As used herein, the term "polyol sugar" means a hydrogenated carbohydrate or sugar alcohol. Examples include xylitol, maltitol, sorbitol, erythritot, lactitol, and isomall.

[0044] As used herein, the term "inflammatory skin disorder" is intended to include within its scope acne vulgaris, acne rosacea, general erythema, poikaderma dc Civcttc. eczema and other conditions resulting from inflammation of the skin,

[0045] As used herein, the term "acne" is intended to include within its scope acne vulgaris and acne rosacea. [0046] As used herein, the terra "food" or "food product" means any solid or liquid material containing nutrients such as carbohydrates, proteins, and fats that are required by humans in order to obtain energy and grow.

[0047] As used herein, the term "beverage" refers to any liquid material containing water as a constituent that provides humans with the hydration necessary for normal metabolism.

[0048] As discussed, the present invention is predicated on a finding that daily consumption of foods high in fructose, oligosaccharides and/or polyol sugars can lead to inflammatory skin disorders such as acne. Recent research by others (8) has suggested an association between a low-glycemic diet with reduced sebum production and fewer acne lesions. This research did not confirm an absence of acne but fewer lesions due to a low-glyccmic diet. Subsequent research (9) in 2010 found no association with acne and a low-glycemic diet. In 2006 published research ( 10) explored gastrointestinal symptoms resulting from the consumption of rapidly fermentable, short-chain carbohydrates (simple sugars). Based on the above evidence of the present research has shown that a low tolerance to specific simple sugars other than glucose in susceptible individuals is linked to acne development rather than a generalised consumption of high-glyccmic foods.

[0049] Modern diets that include a high level of processed foods can lead to an increased

consumption of specific simple sugars or their modified variants. These are present, for example, in wheal, barley or rye grains, natural sweeteners, food additives, thickeners or binding agents. The present research has shown that sensitive people who consume an excess of specific simple sugars arc likely to experience a rapid gastrointestinal response thai precipitates (for example) in an acne flare* up. For people with persistent acne or other inflammatory skin diseases, constant minor irritation of the small intestine due to daily consumption of a range of common foods maintains a simple sugar load higher than can be tolerated for these individuals.

[0050] Certain other food additives (for example MSG) can, during periods of lowered resistance, add to the gastrointestinal discomfort and contribute to effect of the malabsorption of specific simple sugars.

[0051 ] It is proposed that malabsorption in the small intestine of certain groups of short-chain carbohydrates (simple sugars) from both natural or processed sources affects the balance of gut biota. An imbalance in an individual's normal gut biota combined with the consumption of certain simple sugars, promotes the release of endotoxins that are capable of permeating the intestinal mucosa. The endotoxins migrate into the general circulatory system thereby activating an inflammatory response (1 1). This mechanism can lead to inflammation of skin and in susceptible individuals for example mis may present as acne. This effect is pre-empted when individual tolerances for specific simple sugar load have been exceeded. Sensitivity is also exacerbated in these individuals when healthy resistance is lowered (such as hormonal fluctuations, parasite infestation or gastro-intestinal infections etc) or by consuming certain food additives such as MSG that may irritate the small intestine. An inflammatory reaction, such as acne, is likely particularly when any of the above factors coincide.

[0052] As such, the present invention provides a method for preventing or controlling inflammatory skin diseases in a subject, the method comprising administering to the subject a diet that is low in fructose, oligosaccharides and/or polyol sugars.

[0053] A diet that is low in fructose, oligosaccharides and or polyol sugars can be devised by determining the amounts of fructose, oligosaccharides and/or polyol sugars in food producKs) to be consumed by the subject and adjusting the diet so that the total amount of fructose, oligosaccharides and/or polyol sugars consumed by the subject is 40g or less per day. The amounts of fructoee, oligosaccharides and/or polyol sugars in food produces) will usually be determined by determining the amounts of fructose, Crucians, galactans. xylitol, maltitol, sorbitol, crythritol, lactiiol, and isomalt in the food produces).

[0054] The diet that is low in fructose, oligosaccharides and or polyol sugars may comprise natural or commercially available foodstuffs, foodstuffs; that arc specifically formulated for the diet, dietary supplements, and combinations of any of these.

[0055] A suitable diet will typically include foodstuffs:

• containing complex carbohydrates in the form of grains, flakes, flours and meals from cereal grains or vegetables that are low in fructose, oligosaccharides and/or polyol sugars. Examples include flax seed, oats, corn and polished rice; and or

• containing proteins, vitamins, minerals, carbohydrates, (simple and complex), insoluble dietary fibre, and soluble dietary fibre; and/or

• containing simple carbohydrates sourced from fruit, vegetables, grains or similar that have low levels of simple sugars particularly fructose, fructans. oligosaccharides and polyols. For example simple sugars may be selected from the group consisting of, but not limited to, rice syrup, sucrose, lactose, glucose, dextrose, stevia or other sources containing simple sugars with a higher glucose to fructose ratio.

[0056] The diet may comprise food and beverage products that arc specifically formulated and manufactured for use in the diet. Suitable food and beverage products include but are not limited to: breakfast cereals, nutritional bars, snack cakes, chips, shakes, soups, soup mixes, pasta (fresh and/or dried), noodles (fresh and/or dried), ice cream, yoghurt, sorbet, beverage mixes, and beverages.

[0057 J Food and beverage products that are specifically formulated and manufactured for the diet may comprise proteins, vitamins, minerals, carbohydrates, (simple and complex) and incorporate a blend of soluble and insoluble dietary fibres, and fats in appropriate amounts. The food and beverage products will normally be formulated using carbohydrates that are low in simple sugars to avoid gastro-intestinal distress that can lead to acne in susceptible individuals. The food and beverage products will also typically contain levels of fibre, protein and fats to promote fullness and ensure a healthy metabolism.

[0058] In addition to the above nutritional components, the food and beverage products may contain common ingredients such as colorants, prcscrvatives/antioxidants, cmutsifiers and flavorants and the like. Colorants, preservatives antioxidants, emulsifters and flavorants identified as safe for human consumption are referenced in the current edition of Food Chemicals Codex (FCC) published by the United States Pharmacopeia (US?).

[0059] Optionally, the food and beverage products may include pharmacologically active compounds known to have a role in the treatment of acne vulgaris, acne rosacea, general erythema or other inflammatory skin conditions for example poikaderma de Civette or eczema. Suitable

pharmacologically active compounds include but are not limited to: prescription drugs, herbal compounds, derivatives or extracts, vitamins, minerals, fish oil, and omcga-3 fatty acids.

[0060] The manufactured food and beverage products facilitate a convenient dietary regimen to prevent or control acne. To ensure a low daily consumption of simple sugars an individual can create a customised dietary regimen by replacing one or more meals, snacks or beverages with the food and beverage products that have been both nutritionally balanced and specifically formulated to prevent or control the condition.

[0061 ] The manufactured food and beverage products may be used singly or in combination to provide a full serving, which further enhances die subject's ability to customise their dietary regimen.

[0062] The manufactured food and beverage products may be formed by conventional techniques.

[0063] The packaging of a foodstuff suitable for use in the diet may contain information or refer to information regarding the diet Alternatively, or in addition, the foodstu f may be provided or sold in conjunction with information relating to the diet. The information may include an indication that the foodstuff is suitable for use in (he diet and/or for the control of acne. The information may also include details of the fructose, oligosaccharide and/or polyol sugar content of the product.

[0064 j As discussed. I have found that consumption of the diet that is low in fructose,

oligosaccharides and/or polyol sugars may lead to a reduction in the occurrence of acne in a subject or prevent occurrence of acne. Thus, the present invention also provides a method for assisting a subject to prevent or control acne, the method comprising prescribing to the subject a diet that is low in fructose, oligosaccharides and/or polyol sugars.

[0065] The methods of the invention may also comprise providing food produces) in accordance with the formulated diet. The provided food produces) may be packaged meals. Alternatively, or in addition, the provided food produces) may be food beverage products specifically manufactured for the diet, as described earlier. Thus, the method may further comprise providing food produces) for people susceptible to an inflammatory skin disorder.

[0066] Aspects of the method for preventing or controlling acne in a subject may be implemented on a computer. Thus, the present invention also provides a computer-implemented method for selecting food products for a diet for preventing or controlling an inflammatory skin disorder, the method comprising: viewing, on a display of a communication device, a list of food products forming part of the diet; selecting one or more food produces) from the list, using a user interface of the

communication device, to form a daily diet list; calculating the total content of fructose,

oligosaccharides and/or polyol sugars contained in the foodstuffs on (he daily diet list; providing feedback, using the user interface of the communication device, to the subject as to whether the foodstuffs on the daily diet list contain a total amount of fructose, oligosaccharides and or polyol sugars relative to a threshold daily value, and, if the amount of fructose, oligosaccharides and/or polyol sugars in the food product(s) on the daily diet list is below the threshold dairy value, creating a customised daily diet for the subject.

[0067] A simplified schematic diagram of a system 10 for creating a customised daily diet for a subject is shown in Figure 1. The system 10 comprises a communication device 12 having a display 14, a user interface 16 displayable on the display 14, a database 18 comprising a list of food products and information relating to the content of fructose, oligosaccharides and/or polyol sugars in each of the food products, a processor 20 for calculating (he total content of fructose, oligosaccharides and or polyol sugars contained in the food produces) on a daily diet list selected by a subject using the user interface 16 and comparing the total content of fructose, oligosaccharides and/or polyol sugars to a threshold daily value, and providing an output to the subject as to whether consumption of the food produces) on the daily diet list are likely to prevent or control an inflammatory skin disorder in the subject. (006 j In embodiments, the system 100 may be implemented across a communications network such as a local area network or the internet (Figure 2). The system 100 comprises a subject location 102. a communication device 1 4 at the subject location 102, the communication device 104 comprising a display 106 and a user interface 108 displayable on the display 1 8. A server i 10 is located at a server location 1 12 which is remote f om the subject location 102. The server 1 10 comprises a database 1 14 comprising a list of food products and information relating to the content of fructose, oligosaccharides and/or polyol sugars in each of the food products and a processor I I for calculating the total content of fructose, oligosaccharides and/or polyol sugars contained in the food produces) on a dairy diet list selected by a subject using the user interface 16 and comparing the total content of fructose, oligosaccharides and/or polyol sugars to a threshold daily value. A communications link 1 18 between the communication device 104 and the server 1 10 allows the subject to select one or more food produces) using the user interface 108 and receive an output as to whether consumption of the food produces) on the daily diet list are likely to prevent or control an inflammatory skin disorder in the subject.

[0069] The present invention also provides a database of irdbrmation relating to the content of fructose, oligosaccharides and/or polyol sugars in a plurality of food products residing on a server computer, a user interface accessible by a subject and in communication with the database via a communication device, the user interface allowing the subject to select one or more food produces) from the database; a processor for calculating the total content of fructose, oligosaccharides and/or polyol sugars m the selected one or more food produces); and an output for displaying the total content of fructose, oligosaccharides and/or polyol sugars in the selected one or more food produces) to the subject.

[0070] In embodiments, the methods include ordering at least some of the food produces) in the customised daily diet for the subject. In embodiments, the ordering comprises communicating the food produces) order to a merchant remote from the communication device. In embodiments, the ordering also comprises ordering the food produces) from the food produces) order from a production facility; producing the food produces); and shipping the food produces) to the subject

EXAMPLES

[0071 ] Elimination diet for the control of Acne

[0072] A study was conducted to establish the effect of a dietary intervention on subjects with Acne Vulgaris for two week intervals over three sessions in February, May and September 2014 in

Vientiane Lao PD . The typical Lao diet generally consists of little to no wheat flour, breads, pasta or other wheat based products and is therefore an ideal cohort to maximise compliance for this dietary intervention.

[0073 J Independent pre- and post-assessment of subjects for the severity of acne was achieved with the help of the National Centre of Dermatology located in Vientiane Lao PD . A Lao speaking assistant assisted with translation as needed during the dietary interventions.

[0074] Subjects

[0075] Inclusion criteria: Adult males or females with persistent moderate to severe facial acne.

[0076] Exclusion criteria: Current use of isotretinoin or antibiotics, parasite infestation, excessive alcohol intake, illicit drug use, physical or mental illness, diabetes, diagnosed food allergy or intolerance, veganism or vegetarianism. Practical exclusion criteria included impending school or university examinations, or scheduled work or family commitments outside of Vientiane during the intervention period.

[0077] It was anticipated that mast subjects would deviate to some extent from the dietary intervention. For this reason it was critical to select subjects who were most likely to remain compliant with the diet and not supplement with other foods. To reduce the risk of non-compliance the following parameters were followed:

• Although teenagers typically form the largest group of people with acne, adult subjects were chosen as they were more likely to comply with the dietary restrictions within the timeframe.

• Two weeks was determined to be an adequate timeframe to alter intestinal micron iota and provide an opportunity for existing lesions to begin healing Subjects supplied photos at random intervals for several months once the formal intervention concluded and they had established self-compliance to exclude or reduce specific simple sugars from their normal diet.

• Subjects were resident in Vientiane and were recruited using Social Media request in Lao language (Facebook) as well as via word-of-mouth.

• Subjects were excluded from the study if food diaries were not completed or if subjects failed to collect prepared food on schedule every two days.

[0078] Study prxttocol [0079 J Subjects participated in the study at no cost. Agreement with subjects included die collection and analysis of stool samples as well as the provision of photographs pre and post intervention.

Subjects were interviewed (in English and Lao) and an overview of the intervention was described but without specific details of the diet, to avoid subjects modifying current dietary practices before completing their pre-diet diary.

[0080] Subjects supplied a diet diary of all food, drinks and or medicines consumed for 5-7 days prior to the intervention to establish what in their regular foods may have high levels of specific simple sugars.

[0081 ] Stool tests prior to the dietary intervention were analyzed by a local Vientiane clinic for parasite infection. Helminthic treatment was supplied at no cost to subjects prior to the intervention.

[0082] Subjects maintained their current personal cleansing regime. Topical treatments cosmetics if used by subjects were not excluded during the intervention.

[0083] Subjects were asked to only consume prepared foods and agree to exclude any non-prescribed medicines, vitamins or supplements.

[0084] Subjects were assessed at the dermatology hospital prior to the intervention.

[0085] Subjects were counselled (in English and Lao) prior to the intervention including identifying the source and types of simples sugars described in their diet diaries that may be contributing to their acne.

[0086] Every two days a generous amount of prepared meals, drinks and snacks of simple

Lao Western cuisine low in specific simple sugars were collected by individual subjects.

[0087] Prior to collection all prepared foods were photographed.

[0088] Food diaries were completed by subjects on a daily basis and collected at the end of the intervention and included food items not supplied as part of the intervention.

[0089] After the intervention, subjects were taken to a local fresh vegetable market where they were able to photograph foods that were low and high in specific simple sugars to help them with continued self-compliance. (00 0J At baseline end followed up at two weeks, the severity of facial acne was assessed for each subject in person by the same dermatologists (Dr Buddha and Dr Ammala together, or Dr. Ammala alone) from the National Dermatology Centre and photographs were taken.

(0091 J No blood or other tests were taken as part of this intervention.

[0092] Λ Lao-English translator was employed to translate from Lao to English the before-after dermatology reports for each subject.

[0093] Subjects were coached throughout the intervention period, and followed up where needed at monthly intervals during self-compliance.

[0094] Food was prepared for 4-5 subjects per session for a two week period. Foods included were meat, poultry, fish, eggs, home-made soups, and a wide selection vegetables, rice and rice noodles. A live yoghurt preparation was supplied.

[0095] Processed foods including most condiments were excluded due to the usual ingredients containing Mono-sodium Glutamate (MSG) and/or the specific simple sugars excluded as part of this intervention. Home made chilli sauces, live yoghurt, low-sugar commercial mayonnaise were included for variety.

[0096] Subjects supplied their own cooked rice to supplement each meal. [0097] Results and discussion

[0098] Ten subjects participated over three sessions for a period of two weeks per session · in February, May and September 2014 in Vientiane, Lao PDR.

[0099] Two initial subjects in February 2014 were not assessed by staff from the National

Dermatology HospitaL however photos and diet diaries were recorded for this period.

[0 100] The same dermatologist from the National Dermatology Hospital assessed all 8 subjects pre- and two weeks post-diet in May and September. All subjects maintained a diet diary throughout the diet intervention.

[00101 ] Food both fresh and cooked was supplied to subjects every two days with total simple sugars (fructose, oligo-saccharides, polyols) averaging less than 40g per day

• All foods or beverages high in fructose, oligo-saccbaridcs, or polyols were excluded • Processed foods were generally not supplied apart from small amounts of fish sauce or soy sauce used as flavouring

• Generally meals consisted of meat, fish, poultry, salad, vegetables, herbs, chili, fermented fish paste, nuts, dairy, oatmeal, rice, popcorn, soda water, rice noodles, live yoghurt.

• Recommended daily allowance of fibre ( 15-20g) was sufficient via the natural foods provided

• Cooked polished rice was supplied as needed by each subject

• Prepared foods were photographed prior to each pick-up

[00102] Independent reports from the Lao National Dermatology Hospital were provided for each subject, each of which was examined pre- and post-diet Initial examination occurred up to five days before dietary intervention cxKnrnenced. Final examination occurred on last day of diet Subjects were self-compliant after first two weeks. Reports provided below were originally written in Lao language and arc supplied with the English translation.

[0 103] Additional notes by the applicant arc included with each report where background information related to the dietary intervention is needed for individual subjects.

[00104] Subsequent photos provided in the weeks following the two-week intervention are when subjects are self-compliant to stay with the low simple sugar regime.

[00105] Subject 1 Report

[00106] Female, age 24

[00107] Diagnosis: Acne, normal/moderate

[00108] Got acne 2 weeks ago. Acne type: whiteheads, has a group of pustules (pimples that have pus) located at lower side of both cheeks, itchy a bit. So far. have been applying skin cream, Betnevert-N; reel more itchy when applying.

[001 9] Note: Stool exam confirmed strongyloidcs parasite and treatment was provided prior to commencing diet. Subject used a paste of baking soda and other irritants on acne throughout diet period that has inflamed her skin, although it is gradually improving. Menstrual period occurred during diet phase. (001 10] Report after 23 days: Diagnosis: Acne. Compared to before treatment, there are some redness and still some pustules occurred at the lower cheek but no sign of itchiness. As for old acne zone mostly has seen a reduction or disappearance, but a few new pimples revealed at new zones.

(001 1 1 J Photographs of the subject at weeks 0, 2. and 5 are provided in Figure 3.

10 112] Subject 2 Report

[001 13] Male, age 27.

[00114] Diagnosis: Acne

[001 15] Affected by acne more than I year. Used to take regular tablets of Doxycycline Erythromycin, Declofematc Fcxel and some acne skin gel from Hospital 103.

[001 16] Actual examination: Acne scars and few group of pustules (pimples with pus) at both sides of the cheek, with presence of both whitehead and blackhead pimples. Pew small whitehead pimples at the chin.

[001 17] Note: Parasite infection confirmed by stool test and subject was treated for liver fluke prior to cornmencing diet Subject had concluded 2 months treatment with Doxycycline prior to commencing diet with only modest improvement (self-reported).

[00118] Report after 15 days: Diagnosis: Acne. Compared to before treatment, there is some improvement and looking better. Now, remains minor pimples about 2-3 buttons appeared at the right check, face is not so red; some imprint scars after buttons disappeared, only 1 button at the right cheek and no new button.

[0011 ] Photographs of the subject at weeks 0, 2, and 5 arc provided in Figure 4.

[00120] Subject 3 Report

[00121] Female, age 29.

[00122] Diagnosis: normal moderate acne.

[00123] Has been affected by acne more than 20 years and was continuously suffered from then. Acne is papules, whiteheads, acne scars, a few pustules at both side of the cheeks, chin, under the chin. Used to apply with skin cream Corsinc, and have been treated for acne at Niiikonc clinic. (00124] Note: Subject was confirmed tree from parasites by stool exam prior lo diet.

Menstrual period occurred during diet phase. Subject later confirmed acne duration has been for 15 years not 20 as stated in above report.

[00125] Report after 13 days: Diagnosis: Acne. In comparison to before treatment, there are some improvements. Examination: There are still a few papules; whitehead pimple scare has decreased. Old pustules have gone down however one new cyst is showing up at the left check. Overall, no sign of the new pimples.

[00126] Photographs of (he subject at weeks 0, 2, 4 and 5 are provided in Figure 5.

[00127] Subject 4 Report

[00128] Female, age 23.

[00129] Diagnosis: normal/moderate acne.

[00130] Affected by acne for over 10 years. Used to take Vh C tablets, Japanese skin cream. Used facial soap especially for acne and took Japanese supplement tablets.

[00131 ] Actual examination: Some papules, whiteheads, acne scar, some pustules on the forehead, chin, both side of the cheeks.

[00132] A scans parasite confirmed by stool exam. Subject treated prior to diet Menstrual period occurred during diet phase.

[00133] Report after 12 days: Diagnosis: Acne. Compared to the before treatment, it looks much better. Actual examination: Still has some whitehead acne and remains of pit scar acne at both sides of the cheeks, forehead but no pustule, and no new pimples.

(00134] Photographs of the subject at weeks 0, 2, 4 and 5 are provided in Figure 6.

[00135] Subject 5 Report

[00136] Female, age 28.

[00137] Diagnosis: moderate acne. [00138] Affected by acne for 3 years. Used to be treated by injection morning and evening for 5 days (don't know the name of drug) in 2012; after stopping injection for 3 months, acne came back again. Used to suffer from gastritis.

(00139] Present illness: Multiple pit scars on both cheeks and a few papules and pustules.

[00140] Note: Stool exam prior to diet found Ascaris and liver fluke. Treated for ascaris parasite prior to diet but treated for liver fluke end of week I . Follow up stool test for parasite repeated day 14 with clear result. Menstrual period occurred during diet phase. Subject consumed vitamin supplement containing fructose during Week I of diet

[00141] Report after 19 days: Diagnosis: Moderate acne. Ha ve a few red dots, pustules present at both side of the checks, chin and neck. Conclusion: when comparing to the last 2 weeks, now it looks better and improved a lot.

[00142] Photographs of the subject at weeks 0, 2 and 19 are provided in Figure 7.

[00143] Subject 6 Report

[00144] Female, age 21.

[00145] Diagnosis: moderate acne.

[00146] Have had acne for more than 4 years. Acne has been slowly increasing, however, more pimples during menstruation period. Used to be treated at Nitikon clinic for more than I year, acne seems to disappear during the treatment period but it returned when ceased treatment

[00147] Present illness: Multiple pit scars, a few papules, pustules and whitehead came out on both cheeks and forehead.

(00148] Note: Stool test confirmed ascaris parasite. Subject treated before commencing diet.

Menstrual period occurred during 2 week diet phase. Subject had resolved acne by Week 4.

Recurrence by Week 19 after consumption of vitamin supplements containing fructose. Subject provided images for Weeks 4 and 19.

[00149] Report after 19 days: Diagnosis: Moderate acne. Still remains a few pustules in some areas but pustules are not large and some pit scars acne remain. Conclusion: compared to the last 2 weeks, it looks better. (00150] Photographs of the subject at weeks 0. 2, and 1 are provided in Figure 8.

[00151] Subject 7 Report 1001S2] Male, age 32.

[00153] Diagnosis: Pit scar, acne ·+ a few pimples.

[00154] Affected by acne since the age of 15. moderately and continuously. Have used pills, injection, laser treatment and removing pimples head, most recently have been treated at Wutisack clinic for 3-4 months. Present: Pit scars acne with a few pimples.

[00155] Note: Subject had been treated with Isotretinoin 5 years earlier. Mostly scarring on jawline. Subject was confirmed clear from parasite* by stool exam prior to start of diet.

[00156] Report aflcr 19 days: Diagnosis: Acne, grade I ⁺ scar acne. Present: have few pimples with pus (pustules) and pit scars. Conclusion: when compared to the last 2 weeks, there is much improvement

[00157] Photographs of the subject at weeks 0 and 2 arc provided in Figure 9.

[00158] Subject 8 Report

[00159] Female, age 25.

[00160] Diagnosis: Acne, grade 1.

[00161 ] Had acne 3 years ago, continuously. Currently: shown groups of acne scars and few whiteheads pimples and pustules on the face. Has been treated at Wutisack clinic for 3 months.

[00162] Note: Subject had been prescribed Isotretinoin 12 months earlier (Wutisack Clinic). Stool test confirmed liver mike. Subject was treated for parasite prior to commencing diet. Menstrual period occurred during diet phase.

[00163] Report after 1 days: Diagnosis: Acne, grade I . Still has a few pustules on the left cheek, meanwhile at the right cheek and at the chin, remains of pit scars after pimples' disappearance. Conclusion: compared to the last 2 weeks, it looks much better.

[00164] Photographs of the subject at weeks 0. 2 and 21 are provided in Figure 10. [00165] Subject 9 Report

[00166] Female, age 30.

[00167] Diagnosis: Moderate Acne. Still have some red papules shown under the chin.

[001 8] Note: Subject was first to complete the diet in Feb-March 2014. Subject received prepared foods for 5 weeks due to late detection of parasite infection. Stool analysis end week 1 confirmed Hymenokpi* Nana (Dwarf Tapeworm). Analysis end week 3 confirmed Taenia Tapeworm. Treated for parasites beginning week 2 and week 4. Because of parasite infestation, food was supplied for 5 weeks.

[001 9] Note: Subject did not attend an examination prior to commencing the diet, but received an examination after 9 weeks of self-compliance. During examination dermatologist was shown photographs of the subject over a total of 14 weeks for comparison.

[00170] Photographs of the subject at weeks 0. 5 and 14 are provided in Figure 11.

Photographs of the subject at weeks 0, 1 , 2, 3, 5 and 14 are also provided in Figure 12.

100171] Subject 10 Report

[00172] Note: 31 YO Subject particpated in diet for 2 weeks in Feb-2014.

[00173] Note: Mostly acne scarring. Subject was not examined pre-post diet at the Lao National Dermatology hospital. Photos at end of Week 2 show subject with conjunctivitis.

[00174] Photographs of the subject at weeks 0 and 2 arc provided in Figure 13.

[00175] It will be appreciated by persons skilled in the art that numerous variations and/or modifications may be made to the invention as shown in the specific einbodiments without departing from the spirit or scope of the invention as broadly described. The present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive.

[00176] Throughout this specification the word "comprise", or variations such as "comprises' ^* or "comprising", will be understood to imply the inclusion of a stated clement, integer or step, or group of elements, integers or steps, but not the exclusion of any other dement, integer or step, or group of elements, integers or steps. (00177] The reference to any prior an in (his specification is not, and should not be taken as. an acknowledgement of any form of suggestion that such prior an forms pan of the common genera) knowledge.

REFERENCES