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Each BioFlam vegetable capsule contains:

Curcuma longa (Turmeric) extract equiv to dry rhizome 1500mgBromelains 100 mgPapain 20 mgAscorbic acid 40 mgCitrus bioflavonoids extract 50 mgRutin 50 mgd-alpha-Tocopheryl acid succinate 20.66 mg equiv. d-alpha-Tocopherol acid 25IUR,S-alpha lipoic acid 20 mgCopper gluconate 1.79 mg equiv. Copper 250 mcgManganese amino acid chelate 5 mg equiv. Manganese 500 mcgZinc amino acid chelate 10 mg equiv. Zinc 2 mgCyanocobalamin 100 mcg Folic acid 160 mcgPyridoxine hydrochloride (Vitamin B6) 15 mg equiv. Pyridoxine 12.34 mgRiboflavin (Vitamin B2) 50 mg Quercetin 100 mg

• BioFlam offers multiple clinical applications in a single formula. this comprehensive product works via several mechanisms including the modulation of key inflammatory pathways.

• BioFlam contains curcumin c3 complex, a unique turmeric concentrate. c3 complex is produced under strictly controlled conditions throughout cultivation, harvest and manufacturing.

• comprehensive formula to assist in reducing symptoms associated with arthritis, injury and trauma via several mechanisms including, decreasing the inflammatory markers of the arachidonic acid pathway.

• Strictly Practitioner Only

product Highlights:

Dosage: Take 1-3 capsules daily, or as prescribed by a healthcare professional.

pack Size: 60 and 150 vegetable capsules.Warnings: Vitamins can only be of assistance if the dietary vitamin intake is inadequate. If symptoms persist consult your healthcare professional.

* This document is intended for the further education of practitioners. Any statements made on this brochure do not intend to claim a cure for any condition mentioned.

Storage Guide: Store below 25˚C in a cool and dry place.

Provides temporary relief from the symptoms of arthritis, and may reduce inflammation associated with trauma and injury

BioFlam inDicationS: Provides temporary relief from symptoms of arthritis and may help to reduce associated swelling

BioFlam may assist in the reduction of soft tissue swelling, inflammation and bruising associated with trauma and injury

Curcuma longa has been used in traditional Chinese medicine for the relief of menstrual pain and menstrual irregularities

Antioxidant formula

Contains important nutritional antioxidants that reduce the risk of oxidative damage by protecting cells from the effects of free radicals

May assist in the maintenance of normal cholesterol levels and improve LDL:HDL ratios in healthy individuals

May assist in maintaining the health of capillaries and a normal cardiovascular system, and contains nutrients which are inversely associated with high homocysteine levels

May help to maintain brain and nervous system health, and support cognitive and neuromuscular function in healthy individuals

Contains nutrients that support healthy immune function

Assists in wound healing, repair and maintenance of healthy skin

FiGUre. 1 BioFlam may relieVe Joint SWellinG anD inFlammationBioFlam relieves joint swelling and inflammation. Firstly, turmeric, quercetin, bromelain and vitamin E work to decrease inflammatory markers (leukotrienes and prostaglandins). Secondly, bromelain inhibits bradykinin, resulting in reduced vascular permeability and subsequent prevention of leukocyte penetration into the site of trauma.

Leukotrienes Prostaglandins

Leukocytes

Kininogen

Bradykinin

Vascular permeability and pain

BROMELAIN (blocks)

Kinin Cascade

TURMERIC QUERCETINBROMELAINVITAMIN E(block)

BlooD VeSSel lUmen

controls expression of genes encoding pro-inflammatory cytokines, and as a consequence, may reduce production of interleukin 1 (IL-1) and tumour necrosis factor (TNF).6 Similarly, papain, has been demonstrated to reduce both these cytokines, which are released during joint inflammation and promote cartilage degradation.7 Bromelain has been successfully used to speed healing time of bruises and hematomas.1 Curcuma longa has been used extensively in traditional Chinese medicine for soft tissue injury. The proposed mechanism for its action is through inhibition of COX-2 and LOX-5.8 (See Figure. 2)

Curcuma longa has been used in traditional chinese medicine for the relief of menstrual pain and menstrual irregularitiesDysmenorrhoea is often characterised by an elevation in prostaglandin and

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FiGUre. 2 BioFlam may reDUce inFlammatory markerS oF tHe aracHiDonic aciD patHWay. once releaSeD From tHe cell memBrane tHeSe inFlammatory markerS Become inVolVeD in tHe patHoGeneSiS oF DySmenorrHea, artHritiS, inJUry anD traUma

intra-cellular

aracHiDonic aciD

LOX-5

COX-1

COX-2

TXA2

Bromelain (blocks)

QUercetin Vitamin e

(blocks)

LTB4

PGE2

Bromelain (blocks)

tUrmeric (blocks - proposed)

phospholipid bi-layer extra-cellular

DySmenorrHea

Joint pain anD inFlammation

inJUry anD traUma

TRAUMA

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BioFlam may help to reduce joint swelling and provide temporary relief from the symptoms associated with arthritis Bromelain is the collective term for a number of proteolytic and non-proteolytic enzymes. These enzymes are responsible for the anti-inflammatory action of bromelain when used in arthritis.1 Proteolytic enzymes are responsible for protein catabolism and are involved in many physiological reactions, including highly regulated cascades of inflammation. Bromelain exerts some of its broad anti-inflammatory effects via the following proposed mechanisms. Firstly, it increases fibrinolysis via stimulation of plasminogen to plasmin. Secondly, bromelain decreases bradykinin by inhibiting the conversion of kininogen to kinin. Thirdly, it mediates prostaglandin synthesis by inhibiting the enzyme, thromboxane synthetase, thereby reducing pro-inflammatory mediators prostaglandin E2 (PGE2) and thromboxane A2 (TXA2).1-3 (See Figure. 2)

BioFlam contains a therapeutic dose of bromelain to promote anti-inflammatory mechanisms and mediate these biological factors. Through this, bromelain may reduce pain mediation, vascular permeability and therefore swelling and oedema, debris, and immune cell adhesion molecules, which all play a role in the pathogenesis of arthritis.3

aids in the reduction of soft tissue swelling, inflammation and bruising associated with trauma or injury The nutrients contained in BioFlam have been carefully chosen to selectively modulate the triggers, and well established mechanisms of inflammation involved in soft tissue trauma. The arachidonic acid (AA) cascade is the most recognised pathway of inflammation. AA is released from cell membranes and converted by either, cyclooxygenase-2 (COX-2) or 5-lipoxygenase (LOX-5), to series 2 inflammatory prostaglandins (PGE2) and thromboxanes (TXA2), or series 4 leukotrienes (LTB4) respectively. These powerful modulators of inflammation are responsible for pain, vasodilation, erythema, oedema, platelet aggregation and free radical production.4

BioFlam contains quercetin and proteolytic enzymes; bromelain and papain, which may reduce inflammatory markers of the AA pathway. Quercetin has been demonstrated to inhibit COX-2 and effectively reduce prostaglandin and leukotriene synthesis.5,6 It may also inhibit nuclear factor-kappa B (NF-kB), which

ethical innovative dedicated

Contains curcumin C3 complex, a unique turmeric concentrate, extracted using a specialised manufacturing process. C3 complex is produced under tightly regulated conditions throughout cultivation, harvesting and manufacturing processes.

leukotriene levels. Curcuma longa’s mechanism of action for the relief of period pain has been proposed to be a prostaglandin-inhibiting role.9

In addition, the role of oxytocin and oxytocin gene expression appears to play a part in primary dysmenorrhoea.10 Curcuma longa has been found to significantly reduce force and frequency of contractions induced by oxytocin in animal studies.11 These results are suggestive that Curcuma longa may inhibit oxytocin or block oxytocin receptors, resulting in inhibition of pain.9

anti-oxidant formulaThe nutrients within BioFlam have been carefully selected to provide ongoing neutralisation and regeneration of antioxidant systems. Overproduction of reactive oxygen species (ROS) has been linked to the normal aging process, immune activation and is an inducer of inflammation.12

may help to reduce oxidation of lDl cholesterol, maintain normal cholesterol levels and improve lDl:HDl ratios in healthy individualsWhen cells become overloaded with free radicals, oxidative stress transpires, wreaking havoc on lipid membranes. Within the vessel wall, ROS oxidise LDL in the sub endothelial space, initiating events that culminate in the formation of a fibrous plaque.13 BioFlam contains vitamin C, vitamin E, riboflavin and zinc which act synergistically to scavenge free radicals and reduce oxidation of LDLs. (See Figure. 3) An inverse relationship exists between vitamin C blood concentration and total cholesterol and triglycerides. Additionally, higher serum vitamin C results in increased HDL cholesterol.14

1. Nuclear Factor Kappa B

2. Nitric Oxide Excess

3. Eicosanoids & Arachidonic acid

4. Free Radicals

5. Neuro- transmitters & Kinins

6. Immune Responses

7. Homocysteine 8. Acute Phase Reactants

Therapeutic Components in BioFlam

Bromelain PGE2, TXA2 bradykinin, kinin

plasma fibrinogen, fibrinolysis

Curcuma longa

COX-2 PGE2, LOX-5 LTB4

papain cytokines

Vitamin c Redox reactions

histamine immune modulation

CRP

rutin free radicals

D-alpha- tocopherol

Regulates NO synthase

AA, PA2, COX-2, LOX-5

Redox reactions

immune modulation

rS-alpha-lipoic acid

free radicals

copper gluconate

ceruloplasmin, SOD

manganese MnSOD

Zinc free radicals indirectly

neutrophil, natural killer cell, and T-lymphocyte function

Vitamin B12 immune modulation

regenerate SAMe with folate & B6

Folic acid endothelial nitric oxide synthase

regenerate SAMe with B6 & B12

Vitamin B6 endothelial NO biosynthesis

histamine cofactor

cytokines regenerate SAMe with folate & B12

Vitamin B2 NO production

free radicals indirectly

histamine metabolism

Quercetin NFKA nitric oxide (COX-2) enzyme, leukotrienes, prostaglandins

histamine

ANTI-INFLAMMATORY MECHANISMS AND OTHER MODES OF ACTION 8 key BioloGical patHWayS oF BioFlam

1-3,5,7,12,14,15,18-24

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Figure. 3BioFlam protectS tHe BlooD VeSSel Wall anD lDl cHoleSterol From oxiDatiVe DamaGeBioFlam contains important nutritional antioxidants including vitamin C, vitamin E, riboflavin and zinc which act synergistically to scavenge free radicals, reducing endothelium damage and LDL cholesterol oxidation.

Oxidised LDL

Free radical overload

Foam cell

VITAMINS C, E, B2 & ZINC (quench)

BlooD VeSSel lUmen

LDL LIPID POOLFIBROUS PLAQUE

Damaged endothelium Sub-endothelial

space

Figure. 4BioFlam maintainS coGnition anD nerVoUS SyStem FUnction By reDUcinG oxiDatiVe DamaGe anD SUpportinG metHylation WitHin tHe cell BioFlam reduces oxidative damage by supporting the production of enzymatic antioxidants, such as superoxide dismutase (SOD). SOD found in the cytosol is copper and zinc dependent, while SOD in the mitochondria is manganese dependent. Additionally, BioFlam contains nutrients necessary to maintain healthy homocysteine and neurotransmitter synthesis.

SOD

MANGANESE (dependent)

THF

Methlene THF

Methyl THF(folinic acid)

FAD

Cobalamin

Methylcobalamin Homocysteine

Methionine

SAM

SAH

Neurotransmitters

VITAMINS B6, B12 & FOLATE (required for re-methylation)

NucleusMitochondria

Cytosol

Phospholipid membrane

Cell

Free Radicals

SOD

COPPER & ZINC (dependent)

quenches

quenches

VITAMIN B6, FOLATE & ZINC (required)

Biomedica nutraceuticals t/F 1300 884 702 p +61 2 9698 7683 F +61 2 9698 9556 e info@biomedica.com.au www.biomedica.com.au

BioFlam assists in maintaining a normal cardiovascular system, and contains nutrients which are inversely associated with homocysteine levelsBioFlam supports a healthy cardiovascular system. Epidemiological studies have shown inverse associations between antioxidant intake and cardiovascular disease (CVD).15

Elevated plasma homocysteine is an independent risk factor for CVD, and is a marker of inflammation. It has been well established that defects in the methylation cycle contribute to increased homocysteine levels. BioFlam contains important methyl donors; folate, vitamin B6 and vitamin B12 for the re-methylation of homocysteine to methionine.16 (See Figure. 4)

may help to maintain a healthy brain and nervous system, and help to support cognitive and neuromuscular functionBioFlam supports cognitive and nervous system function. It does this via three modes of action.

Firstly, by reducing oxidative damage. ROS damage proteins, lipids, carbohydrates and nucleic acids, which reside in brain tissue.17 Secondly, by assisting normal methylation. Impaired methylation reactions have been proposed to reduce neurocognitive function. Methylation is required for the production of myelin basic protein, neurotransmitter synthesis and the maintenance of homocysteine. Numerous studies have observed an association between hyperhomocysteine and cognitive decline. Thirdly, BioFlam contains vitamin B6, folate and zinc which are essential cofactors for the production of neurotransmitters including serotonin, dopamine and GABA.18 (See Figure. 4)

contains nutrients that are involved in immune mechanisms in the body, supporting healthy immune functionBioFlam contains nutrients that assist in supporting the immune system. Inflammation is a critical physiological process mediated by the innate immune system. In an immune response, inflammatory mediators are produced, which may result in excess inflammation. These mediators are produced by the immune response and include cytokines, prostaglandins, and reactive oxygen and nitrogen species. Subsequently, inflammation may negatively affect immune function.19

Full reference list available on request. BioMedica does not support the use of animal studies. Reference to animal studies may be made when scientific investigation is in preliminary stages.

assists in wound healing, repair and maintenance of healthy skinBioFlam contains vitamins C, B2, B6 and zinc, which play an essential role in collagen synthesis, protein synthesis and membrane structures. These processes are essential for wound healing and skin repair following injury or trauma.20-,22

Selected references 3. Brien, S., et al. Bromelain as a Treatment for Osteoarthritis: a Review of Clinical Studies Evidence-based Complementary and Alternative Medicine, 2004. 16. Kim, M., et al., DNA methylation as a biomarker for cardiovascular disease risk. Plos One, 2010. 5(3): p. e9692-e9692.