In BRUDYLAB we are specialists in medical nutrition based on the human health benefits offered by the Docosahexaenoid acid (DHA). Our goal is to build an offer in dietetic products able to mitigate oxidative stress and inflammation associated to chronic diseases by means of supplementing our diet. Products intended for the oxidative eye protection, to improve human fertility, also to optimize brain function, and to reduce the cardiovascular risk factors associated to an excess of fat in the blood (cholesterol and triglycerides). Food supplements and Dietetic Food for Special Medical Purposes based on the intense antioxidant properties of the DHA-triglyceride (DHA-TG). DHA is a Long Chain Polyunsaturated fatty acid of the Omega-3 family (Omega-3 LCPUFA), which is essential for intellectual and visual development of humans.

During 2014/2015 we have succeeded in getting our European and USA patent approval for the use of DHA-TG as a cell antioxidant. Initially we have centered our basic research in demonstrating the antioxidant activity of this molecule on human cell cultures, to confirm it latter by performing clinical trials.

 

ANTIOXIDANT EFFECT OF DHA-TG (TRIDOCOSAHEXAENOIN-AOX®)

If Brudy has any degree of merit is because we decided to learn from observing the DHA human physiology, with the intention to imitate it. DHA is an absolute need for brain and retina maturation during the fetal development and also in the lactation period when the needs of DHA are much increased.  Needs are more intense during the last quarter of pregnancy and first year of life. The mother is offering DHA to his fetus through the placenta and the umbilical cord that will be continued after delivery through lactation. Mother obtains DHA from her diet, mainly through fish consumption. By analyzing human maternal milk, 87% of DHA present in it can be detected being in the form of triglycerides, and this is the most physiological way to offer DHA to humans thinking in favoring bioavailability.

By analyzing the human maternal milk, we have seen that at least 87% DHA present in it, is in form of triglycerides, and for this reason if we want to get an optimal absorption we should administer it in this chemical form.  When looking at the position to which DHA is located in the milk triglycerides of human maternal milk by means of a chromatography, it can be detected that at least 50% of the DHA is located in the central (Sn-2 Position) because all polyunsaturated are competing to be located in this such position to get a better digestive absorption.

 

Lipases from the saliva, from the stomach and the pancreas are able to break bonds in position 1 and 3 of the triglycerides, liberating the fatty acids located at both ends of the glycerol structure which will be absorbed as free fatty acids. But they are not able to break the bond located in the central position (Sn-2) of the glycerol. The triglyceride is then converted into a monoglyceride, having the DHA molecule in the Sn-2 position, and is being absorbed intact, crossing the entire cytoplasm of the enterocyte to reach the circulating blood in it’s opposite side. Once is in the serum, presence of an LCPUFA in central position stimulates its conversion into a DHA-phospholipid that will be immediately inserted into a cell membrane. A new fatty acid will be randomly inserted in the first position (Sn-1) of the monoglyceride, being converted into a diglyceride, and by placing a polar head in the third position (Sn-3) having a phosphate group and a nitrogen base, the diglyceride is finally converted into a DHA-phospholipid, and is inserted into a cell membrane.

 

OUR PATENTED SYNTHESIS PROCESS

In BRUDY, we convert fish triglycerides into human-like DHA-TG (assuring that DHA is being placed in the central position). By breaking fish triglycerides, and by eliminating all the types of fatty acids (FA) present in fish oil, except DHA: cholesterol, saturated FA, monounsaturated FA, Omega-6 PUFA, and all Omega-3 PUFA except DHA, we finally get a 70% DHA concentrate, almost free of any other FA. By placing this DHA-concentrate into a reactor with glycerol and enzymes, we obtain Tridocosahexanoin (DHA-TG) through a re-esterification process, having DHA placed in the three possible FA attachments in the glycerol structure, and assuring placement of DHA in the central position, as it’s found in the human maternal milk.

 

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OUR PATENT

By synthesizing DHA-TG having the DHA molecule placed in central position, both gastrointestinal absorption and conversion into a phospholipid are favored, and the molecule is immediately deposited into a cell membrane. Trials done in human cell cultures have allowed us to conclude that, the larger is the quantity of DHA present in the cell membrane, the more intense is the oxidative protection offered1. This is related with the 6 double bonds present in each DHA-molecule that can be easily oxidized. The cell protects from DHA oxidation by up-regulating production of glutathione. This is a cell activation to produce larger quantities of glutathione in the cytoplasm, around 200% to 300% more than usual.

 

• Download pdf  (Why Tridocosahexaenoína-AOX® is different from other sources of DHA?)

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DHA Anti-inflammatory2-Anti-angiogenic and anti-tumoral3 activity

LThe Omega-3 PUFA as DHA is, are competitors of Omega-6 PUFA in the cell membranes. A bioavailability dose-response trial of DHA-TG supplementation has shown the effective deposition into red blood cells membrane after 30 days being the intensity of deposition dose-dependent. Chromatography of the membrane shows that a  decreasing content in Arachidonic acid (AA; Omega-6) is compensated with an equivalent increase in DHA. This changes seen in the red blood cell membranes is a true reflection of what is also happening in the rest of body cells.

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INDUCTION PHASE: An Omega-3 LCPUFA enriched diet does facilitate a predominance of these against Omega-6 LCPUFA. When cell destruction occurs, which can be due to multiple causes, cell membrane phospholipids of Omega-3 origin are metabolized to create Prostaglandins and Thromboxanes of the E3 series, and Leukotrienes of the 5 series, showing a clear anti-inflammatory and antithrombotic profiles, and a weak chemotactic activity instead of those generated by metabolites from Omega-6 LCPUFA: Prostaglandins and Thromboxanes from the E2 series, and Leukotrienes of the 4 series, showing clear pro-inflammatory activities.

 

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AMPLIFICATION PHASE: As Corticoids and NSAID’s DHA is also showing inhibitory properties of the kappa-Beta Nuclear Factor (NF-κβ), which is responsible for the amplification of the inflammatory response.4 Its activation derives into a de novo synthesis of new inflammatory mediators as: cytokines (IL-6, IL-8, IL-10), intercellular adhesion molecules (ICAM), vascular cell adhesion molecules (VCAM), Vascular Endothelial Growing Factor (VEGF) and Metalloproteinases, which amplify the inflammatory response and promote neovascularization (angiogenesis) in the affected tissues.

This DHA inhibitory activity on the NF-κβ explains why DHA reduces VEGF synthesis and hinders neovascularization (angiogenesis) and tumor growth.3

 

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DHA IN ONCOLOGY: Supplementing Omega-3 LCPUFA during a period of time previous to starting a chemotherapy cycle it improves efficacy and also reduces the adverse effects derived of it.4 DHA makes more fluid the cell membranes and improves chemotherapy penetration. The glutathione synthesis induced by DHA inside the healthy cells, let them protect from oxidation induced by the chemotherapy drug showing less and less intense adverse effects. Some already published clinical trials on breast cancer,5,6 and lung cancer 7,8,9 are pointing to it.

 

 

 

 

 

 

 

 

 

Bibliographic references:

1. Gassó F, Domingo JC, et al; Docosahexaenoic acid improves endogen antioxidant defence in ARPE-19 cells; 2008 ARVO abstract; Poster 5932/A306.
2. Chen W et al; Anti-inflammatory effect of docosahexaenoic acid on cytokine-induced adhesion molecule expression in human retinal vascular endothelial cells; Invest Ophthalmol Vis Sci 2005; 46: 4342-7.
3. Spencer L, et al; The effect of omega-3 FAs on tumour angiogenesis and their therapeutic potential; Eur J Cancer 2009; 45:2077-86.
4. Nawale Hajjaji, et al; Selective sesitization of tumors to chemotherapy by marine-derived lipids. A review; Cancer Treatment Reviews 2012, jul 29.
5. Bougnoux P, et al; Improving outcome of chemotherapy of metastatic breast cancer by docosahexaenoic acid: a phase II trial; British Journal of Cancer (2009) 101, 1978 – 1985
6. Jiajie Liu, et al; The Role of n-3 Polyunsaturated Fatty Acids in the Prevention and Treatment of Breast Cancer; Nutrients 2014, 6, 5184-5223
7. Concetta Finocchiaro, et al; ffect of n-3 fatty acids on patients with advanced lung cancer: a double-blind, placebo-controlled study; British Journal of Nutrition (2012), 108, 327–333
8. van der Meij BS, et al; Oral nutritional supplements containing n-3 polyunsaturated fatty acids affect quality of life and functional status in lung cáncer patients during multimodality treatment: an RCT; European Journal of Clinical Nutrition (2012) 66, 399 - 404
9. Rachel A Murphy, et al; Supplementation With Fish Oil Increases First-Line Chemotherapy Efficacy in PatientsWith Advanced Nonsmall Cell Lung Cancer; Cancer 2011;117:3774–80.