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MAPP 10 TECHNICAL REPORT Managing Acne Problems Professionally

Active ingredient: Commiphora Wightii

Commiphora Wightii is made from the sap (gum resin) of the Commiphora tree, which is native to India. This tree has been used in Ayurvedic medicine for centuries, and Ayurvedic texts dating back to 600 BC recommend it for treating atherosclerosis.

Commiphora Wightii is the resin of Mukul myrrh tree, a small, thorny plant found predominantly in the rocky, dry regions of India. Commiphora Wightii, the yellowish resin produced in the stem of the Commiphora mukul tree is obtained by tapping the tree throughout the year. This resin is the source of the active components, Z-guggulsterone and E-guggulsterone as well as another eight sterols, acids, several aromatic acids, terpenes and fatty acid alcohols. Some components seem to focus on cholesterol reduction activity, some are anti-inflammatories and some appear to work synergistically.

Today Commiphora Wightii is used for arthritis, lowering high cholesterol, atherosclerosis (hardening of the arteries), acne, weight loss and other skin diseases.

Commiphora Wightii contains substances that lower cholesterol and triglycerides. One of these substances also decreases the redness and swelling that occurs in some types of acne.

Commiphora Wightii is the same genus as Commiphora Myrrha, the myrrh of the bible. The plant has been used in Ayurvedic medicine for centuries. It was cited in the Ayurvedic texts dating back to 600BC for treating atherosclerosis. In most preparations of Ayurvedic medicine in India, serum lipids were found to be lowered by Commiphora Wightii. Commiphora Wightii is one of the components of various formulations of traditional Ayurvedic medicine to treat inflammation, obesity and lipid disorders. Guggul or guggulu (also Commiphora Mukul), more popularly known as Bdellium, is derived from the gummy resinous exudate of a plant closely related to myrrh that is found in arid to semi-arid areas of Northern India, Bangladesh and Pakistan.

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Its oleo-resins are excreted through the skin and mucus membranes, disinfecting their secretions. It is an excellent alternative to non-steroidal-anti-inflammatory drugs (NSAIDs) in its ability to relieve pain, skin and other inflammations as well as promoting healing of the underlying cause. (East West School of Planetary Herbology)

The lipid-lowering effect of Commiphora Wightii may help control cystic acne, and reduce excess production of sebum that may lead to the formation of acne.

The first documented evidence of the anti-inflammatory activity of Commiphora Wightii was reported in 1960 by Gujral. Commiphora Wightii showed inhibitory action against both gram-positive and gram-negative bacteria (International Journal of Pharmacognosy and Phytochemical Research 2014) in the treatment of acne, specifically nodulocystic acne. Reference: Thappa, D.M., Dogra, J. J Dermatol. 21(10): Nodulocystic acne: oral gugulipid versus tetracycline. [Online] October 1994. [Cited: January 18, 2011.] http://www.ncbi.nlm.nih.gov/pubmed. PMID: 7798429

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Clinical Trials

In a trial mentioned in the Journal of Dermatology, this Ayurvedic herb is found to be equally effective as Tetracycline in the treatment of Cystic Nodular Acne. In this trial, 500 mg of extract was given twice a day.

One double-blind clinical trial reported in the Natural Solutions to Healthy Living publication (1994), tested Commiphora Wightii against the antibiotic drug Tetracycline for the treatment of cystic acne. The results showed that Commiphora Wightii compared favorably in its effects to outcomes realized by patients treated with Tetracycline.

In one older 3-month study published in 1994 involving 20 patients suffering from severe acne with nodules and cysts, those given a Commiphora Wightii tablet twice a day had a 68% reduction in inflammatory lesions. This was statistically the same as results experienced by the group randomly assigned to take 500 mg of the antibiotic tetracycline twice daily (65.2% reduction in lesions). Those patients with oily skin responded much better to the Commiphora Wightii treatment. Also of note is that while four of the tetracycline-treatment group relapsed to pre-treatment acne status three months after treatment, only two of the Commiphora Wightii group did.

Nodulocystic acne: oral Commiphora Wightii versus tetracycline.

Abstract

Twenty patients with nodulocystic acne were randomly allocated to one of two treatment schedules: 1) Tetracycline 500 mg or 2) Commiphora Wightii (equivalent to 25 mg guggulsterone). Both were taken twice daily for 3 months and both produced a progressive reduction in the lesions in the majority of patients. With Tetracycline, the percentage reduction in the inflammatory lesions was 65.2% as compared to 68% with Commiphora Wightii; on comparison, this difference was statistically insignificant (P > 0.05). Follow-up at 3 months showed a relapse in 4 cases on tetracycline and 2 cases on Commiphora Wightii. An interesting observation was that the patients with oily faces responded remarkably better to Commiphora Wightii.

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Author information

Department of Dermatology, C.G.H.S., Bajaj Nagar, Jaipur, India

Reference: Thappa DM1, Dogra J. Journal of Dermatology. Published 1994 Oct;21(10):729-31.

Chemical Properties Also known as:

Devadhahupa, Gomme Guggul, Gomme-Resine de Guggul, Guggul, Guggul Gum, Guggul Gum Resin, Guggul Limids, Commiphora Wightii ,Guggulimpid, Guggulsterone, Guggulsterones, Guggulu, Guggulu Suddha, Guglidid, Gugulipid, Gum Guggul, Gum Guggulu, Indian Bdellium-Tree, Indian Bdellium, Indian Guggulipids, Koushika, Mukul Myrrh Tree, Palankasha, Yogaraja Guggul Gum resin

Scientific name:

Commiphora Wightii

Synonyms – Balsamodendrum wightii, Balsamodendrum mukul.

Family – Burseracaea.

Traditionally used for: Orally, Commiphora Wightii is used for arthritis, lowering high cholesterol, atherosclerosis, nodulocystic acne, skin diseases and weight loss.

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Safety:

Possibly Safe… when the prepared extract is used orally and appropriately. It has been safely used in clinical trials for up to 24 weeks (see clinical trials section in this document). Some evidence also suggests that long-term use up to 75 weeks may be safe.

Pregnancy: Likely unsafe…avoid using orally. Commiphora Wightii appears to stimulate menstrual flow and the uterus.

Lactation… Insufficient reliable information available, avoid using.

Effectiveness:

Possibly Safe… Nodulocystic acne: Taking Commiphora Wightii orally is comparable to oral tetracycline in the treatment of nodulcystic acne. Both treatments decreased inflammation and the number of relapses.

Possibly Ineffective…Hypercholesterolemia: taking Commiphora Wightii orally in doses of 3000 & 6000mg per day doesn’t seem to lower total cholesterol or triglycerides, or raise high density lipoprotein (HDL) cholesterol in people on Western diets. It seems to increase low density lipoprotein (LDL) cholesterol by 9 % to 10%.

This is in contrast to studies of Commiphora Wightii in Indian populations, where Commiphora Wightii seems to lower cholesterol, LDL and triglycerides.

Mechanism of Action:

Commiphora Wightii might reduce secretion of sebum and inhibit bacterial metabolism of triglycerides which induces acne. Commiphora Wightii acts as agonists of the pregame X receptor (PXR), estrogen-alpha receptor, and progesterone receptor. The PXR induces the expressions of the cytochrome P450 enzyme CYP3A4.

Preliminary evidence suggests that Commiphora Wightii also has protective effects against drug-induced myocardial necrosis.

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Commiphora Wightii seems to antagonize the farnesoid X receptor (FXR), which reduces the production of bile acids.

Commiphora Wightii also has the thyroid-stimulating activity. It seems to increase the T3 synthesis by increasing conversion of T4 to T3.

Commiphora Wightii seems to have anti-inflammatory activity. Commiphora Wightii might also lower lipoprotein (a) and C-reactive protein. Preliminary evidence also suggests Commiphora Wightii might have antiplatelet and anticoagulant activity.

Adverse Reactions:

Orally, Commiphora Wightii can cause headaches, nausea, vomiting, loose stools, diarrhoea, belching, bloating and hiccups. Commiphora Wightii can also cause hypersensitivity reactions including rash and pruritus. Commiphora Wightii can also cause non-allergic adverse skin reactions. The risk of skin reactions appears to be dose dependant. In one study, the incidence of skin reactions was 3% with a dosage of 1000 mg three times daily, compared to 15% with a dosage of 2000 mg three times daily. The severity of the reactions ranged from pruritus to swelling and erythema of the face to bullous lesions on the lower legs associated with headaches, myalgias and pruritius.

Interactions with herbs & supplements:

Antiplatelet and anticoagulant Herbs and supplements: Preliminary research suggests that guggul might have antiplatelet and anticoagulant activity. Concomitant use of herbs that have constituents that might affect platelet aggregation could theoretically increase the risk of bleeding in some people. These herbs include angelica, clove, danshen, garlic, ginger, gingko, red clover, turmeric and others.

Herbs with Estrogenic Activity: Theoretically, Commiphora Wightii could be additive or antagonistic with other herbs that have estrogenic activity. Some

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of these herbs include alfalfa, black cohosh, chasteberry, flaxseed, hops, ipriflavone, kudzu, liquorice, red clover and soy.

Interactions with drugs:

Antiplatelet / anticoagulant drugs <<interacts with>> Commiphora Wightii Interaction Rating: Moderate be cautious with the combination. Severity: High • Occurrence = Possible • level of Evidence = B Commiphora Wightii might have antiplatelet and anticoagulant effects. Theoretically, taking Commiphora Wightii with other antiplatelet or anticoagulant drugs might increase the risk of bruising and bleeding. Some of these drugs include aspirin, clopidgrel (Plavix), nonsteroidal anti-inflammatory drugs (NSAIDS) such before diclofenac (Voltaren, Cataflam, others), ibuprofen (Advil, Motrin, others) and naproxen (Anaprox, Naprosyn, others), deltearin (Fragmin), enoxapatin (Lovenox), heparin, warfarin (Coumadin) and others. Contraceptive drugs <<interacts with>> Commiphora Wightii Interaction Rating: Moderate be cautious with the combination. Severity: High • Occurrence = Possible • level of Evidence = D Theoretically, concomitant use of large amounts of Commiphora Wightii might increase the adverse effects of contraceptive drugs through estrogen-alpha receptor agonist activity. Cyctochrome P450 (CYP3A4) <<interacts with>> Commiphora Wightii Interaction Rating: Moderate be cautious with the combination. Severity: Moderate • Occurrence = Probable • level of Evidence = D Preliminary research suggests that Commiphora Wightii induce cytochrome P4503A4. Use caution when considering concomitant use of Commiphora Wightii and other drugs affected by these enzymes. Some medications are changed and broken down by the liver. Commiphora Wightii might increase how quickly the liver breaks down some medications. Taking Commiphora

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Wightii long with some medications that are broken down by the liver can decrease the effectiveness of some medications. Before taking Commiphora Wightii talk to your healthcare provider if you are taking any medications that are changed by the liver. Inhibitors that are substrates of CYP 3A4 include atorvastatin (Lipitor) and lovastatin (Lovastaatin). Other drugs that might be affected include some calcium channel blockers (dilitiazem, nicardipine, verapamil), chemotherapeutic agents (etoposide, paclitaxel, vinblastine, vindestine), antifungals (ketoconazole, itraconazole), glucocorticoids, cisapride (Propulsid), alfentanil (Alfenta), fentanyl (sublimemaze), losartan (Cozaar), fluoxetine (Prozac), midazolam (Versed), omeprazole (Prilosec), ondansetron (Zofran), propranolol (Inderal), fexofenadine (Allegra) and numerous others. Diltiazem<<interacts with>> Commiphora Wightii Interaction Rating: Moderate be cautious with the combination. Severity: Moderate • Occurrence = Probable • level of Evidence = B Concomitant oral administration can reduce diltiazembio availability and might reduce therapeutic effects. Taking Commiphora Wightii can decrease how much diltiazem (Cardizem) that the body absorbs. Taking Commiphora Wightii along with diltiazem (Cardizem) might decrease the effectiveness of diltiazem (Cardizem). Estrogen <<interacts with>> Commiphora Wightii Interaction Rating: Major - do not take this combination. Severity: High • Occurrence = Possible • level of Evidence = B Large amounts of Commiphora Wightii might theoretically increase the side effects of estrogen. Some estrogen pills include conjugated equine estrogens (Premarin), ethinylestradiol, estradiol and others. Propranol (Inderal) <<interacts with>> Commiphora Wightii Interaction Rating: Moderate be cautious with this combination. Severity: Moderate • Occurrence = Probable • level of Evidence = B Concomitant oral administration can reduce propranolol bioavailability and might reduce therapeutic effects. Commiphora Wightii might decrease how much propranolol (Inderal) the body absorbs. Taking Commiphora Wightii

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along with propranolol (Inderal) might decrease the effectiveness of propranolol (Inderal). Tamofixifen (Nolvadex) <<interacts with>> Commiphora Wightii Interaction Rating: Moderate be cautious with this combination. Severity: High • Occurrence = Probable • level of Evidence = B Theoretically, concomitant use of large amounts of Commiphora Wightii might interfere with Tamoxifen through estrogen-alpha receptor agonist activity. Some types of cancer are affected by hormones in the body. Estrogen-sensitive cancers are cancers that are affected by estrogen levels in the body. Tamoxifen (Nolvadex) is used to help treat and prevent these types of cancer. Commiphora Wightii could theoretically affect estrogen levels in the body. By affecting estrogen in the body, Commiphora Wightii might decrease the effectiveness of Tamoxifen (Nolvadex). Do not take Commiphora Wightii if you are taking Tamoxifen (Nolvadex). Thyroid Hormone <<interacts with>> Commiphora Wightii Interaction Rating: Moderate be cautious with this combination. Severity: Moderate • Occurrence = Probable • level of Evidence = B Theoretically, concomitant use might interfere with therapy to normalize thyroid function, monitor. Interactions with food:

None known.

Interactions with Lab Tests:

Serum Cholesterol: Commiphora Wightii can reduce serum cholesterol and low density lipoprotein (LDL) cholesterol concentrations by test results.

Serum Triglycerides: Commiphora Wightii can reduce serum triglycerides by test results

Thyroid Stimulating Hormone (TSH): Theoretically, Commiphora Wightii can lower TSH feedback from increased Triiodothyronine (T3). Commiphora Wightii might increase thyroid hormone in the body. Taking Commiphora

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Wightii along with thyroid hormone pills might increase the effects and side effects of thyroid hormones.

Triiodothyronine:by stimulating T3 production.

Interactions with diseases or conditions:

Hormone Sensitive Cancer/Conditions: Some preliminary research suggests that Commiphora Wightii might have agonist effects on estrogen-alpha and progesterone receptors. Women with hormone sensitive conditions should avoid Commiphora Wightii. Some of these conditions include breast cancer, uterine cancer, ovarian cancer, endometriosis and uterine fibroids.

Surgery: Commiphora Wightii has antiplatelet effects. Commiphora Wightii might cause excessive bleeding if used preoperatively. Discontinue use at least two weeks before elective surgical procedures.

Thyroid Disorders: Theoretically, concomitant use might interfere with therapy for hyperthyroid or hypothyroid conditions. Please monitor.

Theoretically, Commiphora Wightii can increase T3 levels

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Chemical Specifications: Appearance and Odor: Light yellow to light brownish-yellow powder; characteristic odor Chemical Name: Commiphora Wightii CAS: See Composition RTECS Number: See Composition Chemical Family: Phytosteroid (guggul) Herbal Family: Burseraacaea Therapeutic Category: Hypolipidemic (guggul) Extract Composition: Commiphora mukul extract (CAS # 93165-11-8; RTECS # GK1188000): 60% Colloidal silicon dioxide ( SiO2; CAS # 112945-52-5; RTECS # VV7310000): 10% Magnesium carbonate (MgCO3; CAS # 546-93-0; RTECS # OM2470000): 30% Buying Specification: Colour: Off white to light yellow Odour & taste: Characteristic Code: CM 25 Botanical Name: Commiphora wightii Plant Part Used: Dried gum exudate Particle Size: 100% through 40 Mesh Loss on drying: NMT 5% Bulk Density(Tapped): 0.30 – 0.80 g/ml Identification: Positive for Guggulterones E & Z by HPLC Assay: NLT 60% for Guggulsterones by HPLC (E & Z only) (As is) Microbiological: Total Plate Count - NMT 1,000 CFU/g Yeast & Mould - NMT 100/g Salmonella & E.coli - Absent Heavy Metals :NMT 10ppm.

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Packaging Specifications

Blister Pack:

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Product Registrations:

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National Pharmaceutical Product Interface:

Product Information: Dosage Form : CAP Product Type : E Manufacturer Code : TFM Supplier Name : Tones Family Health

Pack Information: Code: 705326 NAPPI Suffix : 002 Pack Size : 60.00 Scheduling Status: Currently not scheduled

Presentation:

4 blister packs of 15 capsules

Identification:

Blister pack to state MAPP 10 at the back. Full white size 0 gelatine capsules Registration: Not registered at time of going to print.

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Product Information leaflet:

Front panel:

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Rear Panel:

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Carton Design:

*** Not actual dimensions

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Outer Case:

Pallet Design:

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MATERIAL SAFETY DATA SHEET

Product name : MAPP 10 (Commiphora Wightii 60%)

1. Chemical product & company identification Product name : MAPP 10 (Commiphora Wightii 60%) Company name : Tones Family Health Company address : PO Box 1015, Gillitts 3603 Customer Care. : 082 440 9374 2. Composition/information on ingredients Physical state: Creamish white colour powder (encapsulated) Common name: Guggul Extract CAS – number: N.d.a. EC – number: N.d.a. EINECS – number: N.d.a. INCI: Commiphera Wightii Extract Synonyms: Guggulsterones Impurities: None 3. Hazard identification Physical & chemical hazards: None Environmental hazards: None Adverse human health effects: None Specific hazards: None Main symptoms: None 4. First – aid measures, symptoms and effects Inhalation: None Skin contact: None Eye contact: Irritation Ingestion: Characteristic First aid Inhalation: Fresh air Skin contact: None Eye contact: Rinse with plenty of water Ingestion: None

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5. Fire fighting measures Suitable extinguishing media: Water, CO2

Extinguishing media which must Not be used: None Exposure hazards: None Special protective equipment For fire fighters: None Special fire fighting methods: None 6. Accidental release measures Personal precautions: None Environmental precautions: None Methods for cleaning up: Flush with soap and plenty of Water Methods of recovery: None Methods of neutralization: Not necessary Methods for disposal: Landfill 7. Handling & storage Handling Prevention of exposure: Wear mask and gloves Prevention of fire/explosion: None Precaution for safe handling: Protect from moisture and light Safe handling advice: Good housekeeping practices Storage Suitable storage media: HM – HDPE pail containers Recommendations: Avoid high temperatures and long storage time. Keep container closed Incompatible materials: N.d.a. 8. Exposure controls/ personal protection Engineering measures: N.d.a Specific control parameters Limit values: N.d.a Biological Standards: N.d.a Means for personal protection Respiratory protection: None Hand protection: Wear gloves Eye protection: Required Skin and body protection: None

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Hygiene measures: None 9. Physical and Chemical Properties Physical state: Free flowing powder Colour: Creamish White Odour and taste: Characteristic Optical rotation: Not applicable Acid value: Not applicable Explosive property: None Solubility in water: Partially soluble Decomposition temperature: Above 120°C Vapour Pressure: Not applicable 10 Stability and reactivity Conditions to avoid: High temperatures and high humidity Materials to avoid: None Hazardous decomposition products: None 11. Toxicological information Acute toxicity: N.d.a. Inhalation: N.d.a Ingestion: N.d.a Skin contact: N.d.a Eye contact: N.d.a Chronic long term toxicity: Guggul extract can be considered as non-carcinogenic and practically non-toxic. 12. Ecological information Mobility: Free Solubility: Partially soluble in water Persistence/ degradability: Bio-degradable Bio-accumulation: None Eco-toxicity: Insignificant toxic hazard 13. Disposal consideration Water/ residue: Waste water treatment plant. Regular disposal after washing with water and detergent Package: Disposal in compliance with official regulation 14. Transport information IMCO (sea):N.d.a ICAO/ IATA (air):N.d.a RID/ ADR (land):N.d.a

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U N – number: N.d.a Packaging group: N.d.a 15. Regulatory information Specific international regulation: Complies with natural pharmaceutical regulations Specific national regulation: N.d.a Labelling :N.d.a 16. Other information References: Not available. Other Special Considerations: Not available.

The information above is believed to be accurate and represents the best information currently available to us. However, we make no warranty of merchantability or any other warranty, express or implied, with respect to such information, and we assume no liability resulting from its use. Users should make their own investigations to determine the suitability of the information for their particular purposes. In no event shall The Tones Family Heath be liable for any claims, losses, or damages of any third party or for lost profits or any special, indirect, incidental, consequential or exemplary damages, howsoever arising, even if Tones Family Health has been advised of the possibility of such damages.