See also: Related OurFood News

Subsections

Functional Foods and Novel Foods

Novel Food, Nutraceuticals,Functional Foods, Fast Food, Snacks, Finger Food


Novel Foods

are foods which can be assigned to special types of foods such as genetic modified foods,genetic modified organism and their products, new molecular structures or new technological procedures.Foods which are regulated by the Novel Food Regulation of the European Community have to pass a complicated license procedure.


Functional foods

are foods which have a positive action upon the health of the consumer. The origin of functional food lies im Japan.

Increasing sales of probiotic yoghurt and dairies have boosted the hope of massive profits with functional foods health ingredients, isoflavones, Aloe vera, probiotic bacteria and dietary fibre. It is called " up trading " of the product. Up trading is the rise of quality to achieve better prices.


Functional Food, Nutrition, Nutriceuticals

All these words are used by marketing to boost selling. It is true that fibre can be useful to reduce blood cholesterol or calcium can help to reduce the risk of osteoporosis and vitamins can strengthen the immune system.
The truth is that it does not work.

The consumer is taken to believe that everything is all right when he takes a calcium enriched drink, sometimes with 4 or 5 added synthetic vitamins.

These foods cannot substitute natural nutrition rich in vegetables, fruits and fat reduced meals and whole-meal bread which was the nutrition at the beginning of the 20 th century. The German Nutrition Society (DGE) says that for an average population there is no need of supplements, functional foods or whatsoever when enough vegetables, fruits, fish and whole-meal bread are eaten and low fat nutrition is observed.

Publicity around one-sided modified foods give the consumer a wrong feeling of safety. He things that " he finally can feel well all round " drinking some special stuff of functional drinks which now come on market and does not need to get classic foods which bear all these ingredients together with thousands of other components.
José Lutzenberger a Brazilian Nobel-Price bearer and Franz-Theo Gottwald in their book Ernährung in der Wissensgesellschaft, CAMPUS EXPO 2000 Hannover in their vision about world nutrition say that the global distribution of food and growing modification of food by mighty companies destroy the natural resources of the world.

Many products which are on market and claim to be functional food have only calcium added claiming for health. The supply of Calcium can easily achieved drinking milk or eating yoghurt.
Hannu Salovaara, professor of grain technology at the University of Helsinki says:"It is not new knowledge that foods may also have a healthy activity. In the discussion about Functional Food does one sells only old wine in new tubes?".

Marine omega-3 phospholipids are best for the brain, says study [1]

Omega-3 fatty acids occur as triglycerids, as diglyceride with a phosphate group (phospholipids) or as sphingomyelin, which is derived from sphingosine instead of glycerol. Most phospholipids contain a diglyceride, a phosphate group, and a simple organic molecule such as choline; one exception to this rule is sphingomyelin, which is derived from sphingosine instead of glycerol.

A review by Berge et al. 2012 explains that marine omega-3 phospholipids (n-3 PLs) are phospholipids containing n-3 long-chain polyunsaturated fatty acids (PUFAs) derived from marine organisms. They differ from vegetable phospholipids which do not contain long-chain n-3 PUFAs. Clinical studies were mainly focused on n-3 FAs bound to triglyceridess or ethyl esters. Only recently, health benefits of marine n-3 phospholipids were studied.

There are three main classes of phospholipids: glycerophospholipids (Fatty acids ester-bound to backbone), ether glycerolipids and sphingophospholipids. Glycerophospholipids are the most common subgroup. The most predominant phospholipids in marine sources such as salmon, tuna, rainbow trout and mackerel, is phosphatidylcholine, whereas phosphatidylethanolamine is shown to be the second most abundant. Phosphatidylinositol, phosphatidylserine, lysophosphatidylcholine, and sphingomyelin are found in smaller amounts.

Marine omega-3 phospholipids (n-3 Pls) have nutritional properties with an amazing bioavailiability compared to other forms of omega-3 fatty acids (n-3 FAs). The paper notes that n-3 fatty acids were mainly studied as triglycerides (TGs) or omega-3 ethyl esters, and little attention was given to omega-3 phospholipids (Pls). Berge and colleagues stress the increasing availability of omega n-3 phospholipids which come from sources like krill and fish by-products. Krill oil is extracted from the Antarctic crustacean krill (Euphausia superba), a shrimp-like zooplankton, rich in phospholipid-bound n-3 PUFAs, in particular EPA and DHA. One by-product of the fish industry is fish roe, eggs and the ovaries full of eggs of seafood.

The authors underline that the n-3 phospholipids of fish oil are delivered to brain tissues more efficiently than fatty acids in the triglyceride form. Krill oil has healing effects in case of fatty liver and reduces plasma cholesterol levels and reduces inflammation and arthritis symptoms. The review suggests the use of that marine n-3 phospholipids as functional food used as emulsifiers, as n-3 fatty acids supplement and as beneficial nutritional supplements of phospholipids with their effects.

Bioavailiability of omega-3 fatty acids from krill oil [2]

Bioavailability of omega-3 fatty acids depends on their chemical form. Superior bioavailability was found by Schuchardt et al. 2011 for phospholipid bound omega-3 FA in krill oil. The authors compared the bioavailability of krill oil with the uptake of two fish oils: Re-esterified triacylglycerides (rTAG), and ethyl-esters (EE). The highest incorporation of EPA+DHA into plasma phospholipids was presented by krill oil with 80%, compared to fish oil rTAG 60% and EE 48%. Also a high content of free EPA and DHA in krill oil was found. which might have a significant influence on the availability of EPA+DHA from krill oil, as no free EPA and DHA were determined in the other two fish oils. This may have an influence on the excellent bioavailability of krill oil.

No differences between Krill oil and fish oil regarding effects on metabolic markers and inflammation [3]

Ulven et al. 2011 compared the effect of krill oil and fish oil on serum lipids and markers of oxidative stress and inflammation. Both oils increased significantly plasma EPA, DHA, and DPA content, but no significant differences in changes in any of the serum lipids or the markers of oxidative stress and inflammation between the group supplemented with krill oil and the group receiving fish oil were found. The authors concluded that both oils were comparable as a dietary sources of n-3 PUFAs, even with a lower content of EPA+DHA in krill oil which was only 68,2% of that in fish oil.

The evolution of the final target of nutrition

The final target of nutrition moved between survival, through hunger satisfaction, food safety with deep concern of the consumer and recently a new wave of foods to promote health and healthy living.New concepts like Functional Food,Nutraceuticals , Fortified Foods, Dietary Supplements are created by the industry trying to open new market segments[4].

This has created a great confusion among the consumer resulting in runs after melatonin, abuse of vitamins and sometimes a loss of confidence to retailed foods. Functional Food is not yet well defined. It is intended to close the gap between food and drugs.

Scientific evidence supports the hypothesis that, by modulating specific target functions in the body, diet can have beneficial physiological and psychological effects that go beyond the widely accepted nutritional effects.

Nutritive and nonnutrition components in food have the potential to modulate target functions in the body which are relevant to well-being and health and/or reduction of disease risk [4].


Regulation of functional food

Functional food is not yet regulated by food legislations.The idea behind Functional Food is to make food suited to avoid undernourishment with some special ingredients or to prevent against diseases such as cancer or heart attack.

The main concern of industry and retailers is to find new ways to increase their turnovers. This is why functional food is being on number one in sales promotions.

It should always be kept in mind that normal nutrition is the best guarantee for health. Eat more fruits and vegetables and you get enough fibres and plant sterols. Eat more dairy products and you have no trouble with undersupply of calcium, eat fish and less beef and you get enough iodine.

Functional foods addresses always certain groups of persons which have specific problems as they cover only one or best of all few specific dietary needs. They cannot substitute natural healthy foods.

Definition of functional food

Functional food is currently defined as food of the normal daily intake enriched with substances or organism which have health supporting activity.

They do not help in case of acute diseases, they act on long terms against health risks such coronary diseases or cancer. Sometimes it is unknown at what dose the protective activity takes place, and sometimes the concentration of the active substance in food is not known[5]

Scientific requirements for health claims related to antioxidants, oxidative damage and cardiovascular health [6]

The Panel on Dietetic Products, Nutrition and Allergies (NDA) of the European Food Safety Authority (EFSA) published a draft guidance on scientific requirements for health claims related to antioxidants, oxidative damage and cardiovascular health. The guidance cites the type of evidence for a health claim. The panel takes position to several claims such as:

Beneficial physiological effects: Reference to general, non-specific benefits of the nutrient or food for overall good health or health-related well-being may only be made if accompanied by a specific health claim.

Claims on antioxidant properties of food: These claims are based on the scavenging of free radicals in vitro, however, the physiological effect in humans is not established yet.

Claims on antioxidant status and antioxidant defence: Claims referring to antioxidant status and antioxidant defence have been proposed. The references provided for the scientific substantiation of these claims included in vivo human studies which assessed changes in the overall antioxidant capacity of plasma using methods such as the total reactive antioxidant potential (TRAP), the trolox-equivalent antioxidant capacity (TEAC), the ferric reducing antioxidant potential (FRAP), the oxygen radical absorbance capacity (ORAC) or the ferrous oxidation-xylenol orange (FOX) assays. It is not established that changes in the overall antioxidant capacity of plasma exert a beneficial physiological effect in humans as required by Regulation (EC) No 1924/2006.

Claims on the protection of cells from premature ageing: For these claims, no definition has been provided of "premature aging" or of "healthy aging" in relation to the antioxidant properties of foods, and therefore the claimed effect is considered to be general and non-specific, and thus does not comply with the criteria laid down in Regulation (EC) No 1924/2006.

Oxidative damage, including photo-oxidative (UV-induced) damage
Claims on the protection of body cells and molecules (i.e. DNA, proteins and lipids) from oxidative damage, including photo-oxidative (UV-induced) damage:
The antioxidant properties of foods (measured in vitro), and changes in the overall antioxidant capacity of plasma (measured in vivo as, for example, TRAP, TEAC, FRAP, ORAC or FOX), do not predict a role of the food/constituent in the protection of body cells and molecules such as DNA, proteins and lipids from oxidative damage in vivo, and therefore are not suitable outcome measures for the scientific substantiation of the claimed effect.

Oxidative damage to lipids: The guide proposes Direct measurements of oxidative damage to lipids (i.e. lipid peroxidation) could be obtained in vivo by measuring changes in F2-isoprostanes in 24-h urine samples, which is a better matrix than plasma for this measurement, using gas-chromatography techniques with various detection modes, of which mass spectrometry is preferred. F2-isoprostanes can also be measured using immunoassays. However, lack of specificity owing to possible cross reactions with other prostanoids needs to be taken into account. Measurements of oxidative damage to lipids (i.e. lipid peroxidation) could also be obtained in vivo by measuring oxidised LDL particles in blood using immunological methods (i.e. antibodies) with appropriate specificity. Phosphatidylcholine hydroperoxides (PCOOH) measured in blood or tissue by high-performance liquid chromatography (HPLC) is also an acceptable.

Oxidative damage to DNA: Analyses of 8-hydroxy-2-deoxy-guanosin (8-OHdG) in blood (e.g. lymphocytes), tissue (e.g. skin) and urine have been used to assess oxidative damage to DNA. Free 8-OHdG results from oxidative damage and excision-repair; it may also result from oxidation of free bases or nucleotides, from oxidation of other nucleic acids, and from artefacts during sample work up. Urinary 8-OHdG does not directly reflect DNA oxidation within cells, but could be used in combination with direct measurements of oxidative damage to DNA if appropriate techniques are used for analysis (e.g. HPLC).

Cardiovascular health: Claims referring to cardiovascular health in general need to be accompanied by a specific claim (e.g. claims addressed in sections 5.1 to 5.5 of this guidance). For a health claim on the normal function of the heart, evidence from human studies on specific outcomes (e.g. coronary events) can be used for substantiation.

Claims related to changes in the blood lipid profile: This Claim requires identification of the particular markers which should be considered for the evaluation (e.g. LDL-cholesterol, HDL-cholesterol and triglycerides).

Claims related to blood LDL-cholesterol concentration: Claims for a beneficial effect of the absence (or reduced content) of a food constituent in a food or category of food on LDL-cholesterol concentration have been proposed. Substantiation may be based on evidence for an independent role of the food constituent in increasing LDL-cholesterol concentration.

Claims related to blood HDL-cholesterol concentration: Evidence for a sustained effect with continuous consumption of the food/constituent over longer periods of time (e.g. eight weeks) should also be provided.

Claims on the reduction of blood pressure: The scientific evidence for the substantiation of health claims on the maintenance of normal blood pressure can be obtained from human intervention studies showing a short-term (e.g. three to four week) reduction in systolic blood pressure, or a reduction in diastolic blood pressure if accompanied by a reduction in systolic blood pressure as compared to a food/constituent which is neutral with respect to the claimed effect, or exceptionally to no treatment.

Claims on endothelial function: Endothelial function per se is not sufficiently defined for a scientific evaluation, because endothelium-derived active factors play a role in the maintenance of several functions of the vascular system. These include vasomotion, smooth muscle proliferation, thrombosis, inflammation, coagulation, fibrinolysis and oxidation, which can be assessed by indirect methods.

Claims on reduced platelet aggregation: Decreasing platelet aggregation in subjects with platelet activation during sustained exposure to the food/constituent (e.g. four weeks) would be a beneficial physiological effect.

Claims on homocysteine: Scientific substantiation of this claim may come from the well established role of a food in contributing to the remethylation or degradation of homocysteine (e.g. some vitamins), or can be obtained from human intervention studies.

Disease risk reduction claims: Reduction in blood LDL-cholesterol concentration, therefore, is considered beneficial in the context of a reduction of disease risk claim for CHD, and reduction in (systolic) blood pressure is considered beneficial in the context of a reduction of disease risk claim for CHD and stroke. Therefore, human studies on the risk of CHD are required for the substantiation of these claims in order to validate the association between these variables and the risk of disease in the context of a particular nutritional intervention.

The guidance will be an invaluable source for those wishing to make a health claim for their products, since they can focus resources on studies that will be most acceptable to the regulatory authorities.

FOSHU: Functional Foods in Japan

In the seventies there were Japanese researches on food which discovered special activities of some components. These substances were later on used in pharmacology. That is how functional food had its origin. In Japan three functions of food were reported.:

1- Nutritional value: The primary function is to help the body to keep alive.
2- Taste: The secondary function of food is to satisfy the feeling of taste and smell
3- Activity on the physiological system: The third function of food is to strengthen and modulate the physiological system. This activity is to be claimed as functional food.

In Japan functional foods are grouped under FOSHU (Foods for Special Dietary Uses).
The products with functional claims must be authorized by the Japanese food administration. There are only few products which are FOSHU authorized.

A great variety of foods with functional claims are not authorized as the produce say that costs to make necessary tests are to expensive, the time it takes to make these test is to long and therefore unfriendly to innovations, the higher concentration of the functional ingredient increases the price and alters the taste.

Health claims are scientific and not understandable for an average consumer. Therefore not authorized functional foods are tolerated by Japanese authorities.

The development of functional foods must be considered critically as it misleads the consumer. A broad activity of commercials takes the consumer to by a specific food in the hope to be fed all round with all other components he can only get with a well-balanced nutrition.

Foods with Health Claims Foods for Specified Health Uses in Japan

Foods with Health Claims Foods for Specified Health Uses (FOSHU) and Foods with Nutrient Function Claims have been regulated by the Ministry of Health, Labor and Welfare since 2001, updated in 2005.

FOSHU foods are the only type of foods that can carry some kind of a health claim in Japan. They have only a small market because of high costs for their approval which includes human clinical trials. Therefore functional foods and dietary supplements are marketed without labelled health claims.

This situation caused that unregulated functional foods were put on market, such as conventional food and beverages fortified with health ingredient to promote both general and specific health conditions without label health claims. [7]


Ingredient Healt claim status
Alpha lipoic acid (ALA)   Health food
CoQ10   Health food
Collage   Health food
Ceramide   health food
Pracenta   Health food
Hyaluronic acid   Health food
Isoflavones   Health food
Carnitine   Health food
Essential fatty acids (EPA, DHA, DPA)   Health food
Tocotorienol   Health food
Astaxanthin   Health food
Creatine   Health food
Green tea drink Kirin, seasonal allergy Healt Food
     
Soymilk Kibu soy peptide, Health food
  energy boost  
     
Plant lactic acid drink Kagome lactic acid bacteria, Health food
  gastrointestinal health  
     
Pucera cookies Olio linolenic acid, Health food
Ingredient Healt claim status


The other is regulated functional foods, known as FOSHU (Foods for Specific Health Uses). FOSHU is the government approved foods that carries specific health claims on product labels, ranging from gastrointestinal health to lowering cholesterol.


Healt claim Ingredient status
Gastrointestinal health    
  Oligosaccharides / Prebiotics FOSHU
  Dietary fiber FOSHU
  Lactic acid bacteria, probiotics  
Lower cholesterol    
  Soy protein/ soy globulin FOSHU
  Soy phospholipds (CSPHP) FOSHU
  Low molecule alginic acid FOSHU
  Plant sterol/stanol esters FOSHU
Lower hipertension    
  Gama-aminobutiric acid GABA FOSHU
  Vinegar acid FOSHU
  Lactololi-peptide  
  Eucommia leaf glycoside FOSHU
  Wakame peptide, Undarine pinnatifida FOSHU
  Marine peptide, sardine peptide  
Lower blood glucose    
  Wheat albumin FOSHU
  Guava Polyphenoles FOSHU
  Indigestible dextrin FOSHU
Lower serum triglycerides    
  Diacylglycerol FOSHU
  Plant sterol FOSHU
  Medium chain fatty acid FOSHU
  Globin protein enzyme disintegrated FOSHU
  Green tea catechin FOSHU
  EPA and DHA acid FOSHU
Better mineral absorption    
  Calcium,citric acid, malic acid (CCM) FOSHU
  Casein phospho peptide (CPP) FOSHU
  Heme-iron FOSHU
Improve dental health    
  Xylitol,phosphate-hydro calcium, funoran FOSHU
  Phospho acid olygosaccharides calcium FOSHU
  Recaldent (CPP-ACP) FOSHU
Improve bone health    
  Soy isoflavones FOSHU
  Fructo Oligosccharides FOSHU
  Vitamin K2 FOSHU
  Milk Basic Protein MBP
Healt claim Ingredient status



Probiotics []

According to FAO/WHO Guidelines for the evaluation of probiotics in food 2002 probiotics are live microorganisms which when administered in adequate amounts confer a health benefit on the host.

Probiotic health claims are often confusing and controversial [8]

Morrow and Kollef 2008 state that probiotics are not marketed as pharmaceuticals and no rigorous scientific documentation of their efficacy are needed for placing them on market. Many probiotic health-claims are based on confusing and controversial studies. The authors write that new understanding of the mechanisms of action of probiotics may lead to a more logical framework of future trials.

Controversity about probiotic drink Actimel from Danone [9]

The marketing of Actimel [10]

According to Spiegel Online Danone spent 50 Million Euro from January to October 2008 as marketing budget for Actimel in Germany counting for a volume of sales of about one Billion Euro worldwide per year. Actimel helps to strengthen the body's defence mechanisms, exceeded €1 billion in sales.

Flourishing global market of probiotics [11]

Khan and Ansari in a monograph of 2007 stresses the growing interest in self-care and the recognition of the link between diet and health of the consumer, providing a flourishing market for functional foods and probiotic products which represent a wealth of marketing opportunities. The authors provide a summary of research on the health benefits of probiotics and information regarding the global market of probiotics.

Functional foods with unclear benefits suffer the impact of financial crisis [12]

According to UK Financial Times the so-called "functional foods" movement with exotic products such as flavour and vitamin enhanced waters may be severely hit by the financial crisis leaving less money to be spent by the consumer.

Nutritional cosmetics [13]

A yoghurt with ingredients like borage oil, vitamin E and green tea antioxidants It is supposed to "nourish" the skin, while claiming that it "nourish your skin from within" entering the field of nutritional cosmetics. Experts say that beauty brands are out of place at the food department of a supermarket. A pharmacy distribution suits better for products with undefined claims.

Confusing range of fruit drinks, with and without milk [14]

Special marketing pressure is exerted on drinks for children. A confusing constellation of claims like GM free, no preservatives added no whole soy milk, but soy protein isolate is used to avoid bitter taste, vitamins and calcium are added.

Fruit flavoured waters and ice cream drinking yoghurts and even chewing gum with special health claims are being marketed by global food companies.

Other drinks call on the negative calorie effect (thermogenesis) of epigallocatechin gallate EGCG found in green tea extract which is supposed to speed up the metabolism and increase energy expenditure when taken together with caffeine. These drinks burn 60 to 100 calories, says the producer.

A cup of green tea and a cup of coffee during the day have the same effect heralded by the producer of sophisticated drinks. [15] [16]

Functional properties of feijoa extract [17]

The functional properties of aqueous extracts of blueberry, strawberry, green kiwifruit and feijoa towards the growth of probiotic and pathogenic bacteria were found by Hap and Gutierrez 2012 to have growth-stimulating effects on the probiotic bacteria, except with Bifidobacterium longum. Pathogen were inhibited. Feijoa extract was most effective against Listeria monocytogenes and Bacillus cereus. The authors highlight the importance of aqueous extracts of these fruits as functional ingredients in food. These extracts may become interesting to control the growth of pathogens and stimulate the growth of probiotic bacteria during production and storage.

Feijoa, guayabo, goiaba

The feijoa (Feijoa sellowiana Berg, new name Acca sellowiana (O.Berg) Burret) is native to extreme southern Brazil, northern Argentina, western Paraguay and Uruguay where it is common wild in the mountains. It is closely related to guava. In Uruguay, it is called, in Spanish, guayabo del pais. It has been nicknamed "pineapple guava", "Brazilian guava" and "fig guava". The term "guavasteen" has been adopted in Hawaii. The fruit is rich in water-soluble iodine compounds. The percentage varies with locality and from year to year but the usual range is 1.65 to 3.90 mg/kg of fresh fruit. Most types are high in pectin, so that 3 lbs (1.4 kg) of jelly can be made from 1 lb (.45 kg) of fruit. Ascorbic acids content varies between 28 to 35 mg/100 g edible portion. [18]

Stability of green tea extract in biscuits increases with reduction of pH of the dough [19]

Sharma and Zhou 2011 describe the inclusion of green tea extract in biscuits as a mean to increase tea catechins in pastries. Catechins proved to be stable in dough but decreased during baking, and increased as the concentration of green tea extract was increased in the biscuit dough. The stability of catechins could be improved by reducing the pH of the dough using less alkaline baking powder, sodium bicarbonate, and ammonium bicarbonate.

Herbal ingredients

Herbal ingredients have been used as food flavoring for hundreds of years. Many herbs are used in pharmacy and are regarded as natural remedies looking for new market segments functional foods rediscovered the value of these herbs when used as ingredient of food.
Consumer are increasingly looking for self-medication using drugs on herbal extract basis available in supermarkets and practicing disease prevention through diet.
Possible functional ingredients are:
Vitamins
Minerals
Essential fatty acids, such as omega 3 and omega 6 fats and oils
Amino acids
Aloe vera to nourish and hydrate the body
Echinachea to support the body's immune system

Fibre

A new fibre is Psyllium which grows in India is told to be very effective to lower cholesterol.
Other polysaccharides with fibre activities are beta-gulcane, pectin, guar gum, inulin, chitosane,cyclodextrine.
Oligosaccharides
Green tea extract has powerful anti-oxidant properties
Tocotrienols
Alpha lipoic acid
Sugar alcohols
Gingko biloba claimed to relieve stress and aid mental alertness.


Oligofructose and body weight reduction strategy

Oligofructose is a carbohydrate-based dietary fiber extracted from chicory roots (Cichorium intybus var. sativum) Fresh chicory root contains, by dry weight, 68% inulin, 14% sucrose, 5% cellulose, 6% protein, 4% ash, and 3% other compounds It is being proposed as a sugar and fat substitute to reduce energy intake of obese people.

Verhoef, Meyer and Westerterp 2011 report that taking oligofructose 8 grams twice daily during 13 days, reduces the energy consumption by 10%, concentrations of the satiety hormones PYY and GLP-I were increased, feelings of hunger and satiety remained unaltered. [20]

In an earlier study, oligofructose (8 g ingested twice daily = 16 g/day in total) were found by Cani et al. 2006 to increases satiety, reduces hunger and food consumption. The authors proposed oligofructose supplements to treat obesity. [21]

Parnell and Reimer 2009 report that 21g oligofructose supplementation per day reduces body weight and improve glucose regulation The supplementation reduced the hunger inducing hormone ghrelin, and increases the peptide YY (PYY), a hormone which reduces appetite, resulting in weight loss. [22]


Inulin [23]

According to Roberfroid 2005, inulin is a generic term to cover all beta 1-2 bond linear fructans. Chicory inulin is a linear beta 1-2 fructan, its partial enzymatic hydrolysis product is oligofructose. The beta-configuration of the anomeric C2 in their fructose monomers makes inulin resistant to digestion by intestinal enzymes.

According to Shepherd and Gibson 2006, dietary fructose induces abdominal symptoms, known as irritable bovel syndrome in patients with fructose malabsorption. The authors explain that free fructose can be present in foods like fruits and honey; as a constituent of sugar or as fructans. About 30–40% of people in Central Europe suffer from fructose malabsorption. Inulin is a fructan and may lead to increased flatulence and loose stools in those with fructose malabsorption. Therefore the authors recommend to keep the consumption of fructan less than 0.5 grams/serving for people which suffer from fructose malabsorption. [24]

Fructans, Oligofructose and short-chained carbohydrates were measured by Muir and colleagues in vegetables and fruits [25] [26] and in grains and cereals. [27]

Isoflavones

Phytoestrogens [28] [29]

Dietary phytoestrogens are plant-derived nonsteroidal compounds with weak estrogen-like activity. Most phytoestrogens in foods are inactive which are transformed into a steroidal structure similar to estrogens by enzymes of the gastrointestinal duct. Phytoestrogens are subdivided into 4 main classes: isoflavones, lignans, cumestrans and phytosterols, of which the isoflavones and the lignans are the 2 the most important.

Phytoestrogens exposure and reproductive consequences [31]

Phytoestrogens have been promoted as healthy dietary supplements and foods, such as soybean-derived foods, rich in the isoflavones genistein and daidzein. These isoflavones are also found in soy-based infant formulas.

Phytoestrogen groups: Isoflavones (genistein, daidzein, glycitein, formononetin), flavones (luteolin), coumestans (coumestrol), stilbenes (resveratrol) and lignans (secoisolariciresinol, matairesinol, pinoresinol, lariciresinol). Isoflavones are found at high concentrations in soybean products whereas lignans are found in flax seed, coumestans are found in clover, and stilbenes are found in cocoa- and grape-containing products, particularly red wine.

Jefferson, Patisaul and Williams 2012 write that many studies provide evidence that phytoestrogen exposure can impact the reproductive health, depending on the dose, route of exposure, and the timing of exposure beginning in the early prenatal period. The authors caution that more phytoestrogens are recognized or developed as therapeutic compounds, and are placed on the food market as supplements. The researchers call for careful study of their the effects on the reproductive system, as negative effects are known.

Soy isoflavones supplement

Soy foods are well balanced and are ingredients of a wide rage of products. Daniel Doerge and Daniel Sheehan oppose the decision of the FDA to approve a health claim that soya reduces the risk of heart disease.

According to Doerges and Sheehan the isoflavones of soya (genistein, daidzein and glycitein) have similar effects to the female hormone oestrogen. Soy oestrogen can lead to health problems in animals including altering sexual development of foetuses and causing thyroid disorders. Although soy is thought to protect against breast cancer, some studies show that some substances may increase the chances of breast cancer which uses oestrogen-type hormones for growth.

The claims of soy isoflavones supplement are to compensate the declining oestrogen levels and thus relieve menopausal symptoms, such as hot flashes, as well as decrease the risk of heart disease and osteoporosis, without promoting breast cancer. However, exactly what effect concentrated isoflavones have remains unclear. That is why normal soy food or soy powder is beneficial but isolated soy oestrogen supplements are being looked upon with scepticism.

Isolated Isoflavones not without risk [32]

The Federal Institute for Risk Assessment (BfA) stresses that soy and red clover contain isoflavones. These phytoestrogens }indexPhytoestrogenscan have a hormone-like effect. There are reports that Asian women who follow a traditional diet and regularly consume soy products scarcely suffer at all from menopausal complaints.

The Bfa, however, reminds that a distinction must be made between whether bioactive compounds are ingested naturally from food or in isolated, fortified form via food supplements. In Germany for some time now food supplements with isolated isoflavones have been available on the market as an alternative to the pre-scribed hormone replacement therapy for menopausal complaints. The products are claimed to be efficacious natural products on menopausal complaints as well as other advantageous health effects on the heart, bones and breasts without any side effects.

Adverse effects of soy/red clover-containing products do not refer to uniform sets of symptoms and point to allergic reactions and/or other causes, perhaps to the basic symptoms of the menopausal complaints of the persons concerned. The adverse effects are linked to various food supplements including ones which contain or contained other possible causal substances besides isoflavones, like nicotinic acid - a source of niacin.

The health assessment of isoflavone-containing food supplements, made by the German Federal Institute for Risk Assessment (BfR) found that the assumed positive effects of isolated isoflavones on menopausal complaints Toxicological studies showed that high does of isoflavones, impair the functioning of the thyroid gland and can change mammary gland tissue. It cannot be ruled out that these estrogen-like effects could promote the development of breast cancer.

At the present time, the claimed favourable effects of isolated isoflavones must be deemed to be not sufficiently scientifically substantiated.

The BfR advises against the long-term intake of these products given the unproven positive effects and the serious health consequences for meno-pausal women which cannot be ruled out. BfR concludes that the safety of products containing isolated isoflavones on a soy or red clover basis has not been sufficiently proven. In addition, BfR concludes that there are health risks with low probability from food supplements of this kind for women during and after menopause.

Phytoestrogens in foods of animal origin [33]

Gunter Kuhnle and colleagues 2008 assessed the phytoestrogens content of foods of animal origin. The study focused on the isoflavones biochanin A, daidzein, formononetin, genistein, and glycitein; the lignans secoisolariciresinol and matairesinol; coumestrol; equol; enterolactone; and enterodiol in 115 foods of animal origin.

The authors detected phytoestrogens in all foods analyzed; the average content was 20 microg/100 g of wet weight (isoflavones, 6 microg/100 g; lignans, 6 microg/100 g; equol, 3 microg/100 g; and enterolignans, 6 microg/100 g). In infant soy formula, 19 221 microg/100 g phytoestrogens were detected (compared to 59 microg/100 g in non-soy formula). According to the study phytoestrogens in animal products are low when compared to foods containing soy, but the range is similar to that of many commonly consumed vegetables.

The controversy of phytoestrogens

The authors point out that, despite their potentially beneficial effects, dietary phytoestrogens may be involved in the occurrence of chronic diseases. Studies cite hormone-dependent cancers, cardiovascular diseases, osteoporosis, menopausal symptoms, male infertility, obesity and type-2 diabetes. the compounds were found to be biologically active even at low levels in humans with the gene variants of the estrogen receptor (ESR1 and NR1, sex-hormone binding globulin (SHBG), and probably aromatase (CYP19). [34] [35] [36]

New analysing technique

Kuhnle and colleagues present a modified technique to analyse phytoestrogens in food samples and publish their content in foods of animal origin.

The authors stress that actual data limited to isoflavones and ligans in fruit, vegetables, nuts, and seeds and very little concerning animal foods, may lead to an underestimation and misclassification of dietary exposure. They emphasize, therefore the need for chromatographic analytical systems using as many labeled standards as possible and urges not to rely only on single focused analytical methods based on immunofluorescence.

They conclude that reliable information on the phytoestrogen content in animal foods is required to assess dietary exposure and disease risk in epidemiological studies.

Soy foods and reduced fertility

The soy genistein may damage human sperm [37]

Isoflavones that exert an oestrogen-like effect like genistein, daidzein, and glycitein from soy, are dietary oestrogens that are a natural alternative to hormone replacement therapy and are supposed to slow prostate and breast cancer.

Lynn Fraser and colleagues 2005 reported that even tiny doses of these natural compounds can cause human sperm to lose fertility. Fraser says that genistein combined with other environmental oestrogens, such as 8-prenylnaringenin (found in hops),and nonylphenol that is found in industrial products like paints, pesticides and cleaning products, the damage to fertility increases.

The combination of these chemicals get effective at capacitation, the stage when a sperm acquires the ability to fertilise an egg. The chemicals cause the release of the enzymes that enable the sperm to penetrate the coverings of the egg. When the release happens before the sperm finds the egg cell, it looses the capability to penetrate the egg.

Fraser says that the premature capacitation is stimulated by both genistein and nonylphenol which trigger the production of the messenger AMP which is more likely to affect sperm when they reached the female tract where they would be preparing to fertilise eggs. Maternal exposure to the compounds is therefore probably more important than paternal exposure.

Soy products were found to reduce the concentration of sperm particularly in overweight or obese persons [38]

A study by Jorge Chavarro and colleagues 2008 found that high consumption of soy isoflavones could affect fertility.

Soy foods like tofu, tempeh, soy milk and other non-daily alternatives, energy bars, and vegetarian products using soy as a meat analogue were included in the study. Half a serving is said to be equivalent to one cup of soy milk or one portion of tofu, tempeh, or soy burgers every other day.

High intake of aan average of half a portion of soy foods per day reduced the sperm concentrations of 41m less per ml. The normal sperm concentration range is 80-120m per ml.

High sperm count and overweight

The effect on sperm concentrations seemed to be more pronounced in men who already had higher or normal sperm counts. Overweight people presented a more pronounced effect, because higher body fat produces more oestrogen than slimmer men.

Chavarro and colleagues concluded that men should avoid eating too much soy if they are planning a family.

The authors stress, however that Asian populations consuming high amounts of soy foods presented no reduced fertility or other health problems.

Genetic susceptibility to estrogen from soy products [39]

Although the importance of estrogens in male reproduction is indisputable, little attention has been paid to the role of estrogen receptor (ER) gene mutations in male infertility. The authors found an association between higher TA repeat number (genotype A) and lower sperm production. In line with this observation, normospermic subjects with genotype A had a significantly lower mean sperm concentration with respect to men bearing genotype B with shorter TA alleles and a lower total sperm count.

The authors concluded that specific allelic combinations of the ERalpha, which confer a stronger estrogen effect, may negatively influence human spermatogenesis.


No cardiovascular benefit from soy isoflavones [40]

Garrido and colleagues followed the suggestion that isoflavones protect the cardiovascular system, in part by improving lipid profile. They examined the effect of 12-weeks soy isoflavone supplementation on lipoprotein status and platelet thromboxane A2 receptor density.

Blood pressure, body mass index, subcutaneous fat, insulin, serum lipoprotein, sex hormones and sex hormone-binding globulin did not differ among experimental group and placebo group. However, platelet thromboxane A2 receptor density declined significantly in the experimental group, remaining mostly unchanged in the placebo group. The change in platelet thromboxane A2 receptors correlated negatively with isoflavones serum concentration.

The authors concluded that there were no cardiovascular benefit from soy isoflavones. The beneficial effects of isoflavones in menopausal women could be more related to platelet function than to improving classical cardiovascular risk factors.

Phytoestrogens protect against lung cancer [41]

Margaret R. Spitz and colleagues assessed the role of phytoestrogens and reduction of risk of lung cancer. They found that total phytosterols, isoflavones, lignans, and phytoestrogens were each associated with reductions in risk of lung cancer ranging from 21% for phytosterols; to 46% for total phytoestrogens from food sources onlyfor men abut only total phytoestrogens from food sources were effective against lung cancer in women. There were also significant joint effects found between hormone therapy use and phytoestrogen intake, such as the lignans enterolactone and enterodiol in women.

The authors concluded that their data provide further support for the limited but growing epidemiologic evidence that phytoestrogens are associated with a decrease in risk of lung cancer, however, more studies on this subject are needed.

Other bioactive food ingredients are

Phosphatidylserine and Garlic.

Aloe vera

Aloe vera (Linné) was taxonomically renamed by Miller in 1768 as Aloe barbadensis (Miller). Both names relate to the same plant. There are about 300 species of Aloe, but only Aloe vera and Aloe arborescens bear compounds with health related effects. The most important of these is the mucopolysaccharid acemannan. [42]
Aloe latex and aloe gel can be derived from Aloe vera.

Aloe latex (or aloe juice)

It is the bitter yellow exudate from the outer skin of the leaves. Its active compounds are the anthraquinone glycosides aloin A and B. Aloe latex is laxative.

Aloe gel

: It is often sold as powder. It is the colourless gel contained in the inner part of the fresh leaves. Important polysaccharides are pectins, cellulose, hemicellulose, glucomannan, acemannan and mannose derivatives. The most important of these compound is acemannan. Aloe gel is often commercialised as powdered concentrate.

Effects in burn wound healing [43]

Maenthaisong and colleagues 2007 say that aloe vera might be an effective interventions used in burn wound healing for first to second degree burns, and call for more studies.

Cautions against specific effects [44]

Aterton in 1998 calls for caution against complementary treatments like chronic venous leg ulcers with oral or topical application of Aloe vera that may aid healing.

Aloe vera gel

It is a preparation of leaf pulp from the parenchymal tissue of the plant Aloe vera (Liliaceae). Aloe vera gel contains carbohydrate polymers, such as glucomannans or pectic acid, and various vitamins and essential amino acids, as well as other organic and inorganic compounds. This agent has been used internally or externally for sunburn, skin problems, insect bites, ulcers, arthritis, constipation, and as an immune system enhancer.

Antitumor activity [45]

Aloe-emodin: It is a compound of the family of anthraquinones, with anti-inflamatory andf anticancer effects.

Aloe-emodin (1,8-dihydroy-3-[hydroxymethyl]-anthraquione) purified from Aloe vera leaves has been reported to have antitumor activity. The authors found that aloe-emodin delayed the number of cells entering and exiting DNA synthesis (S) phase in cells indicating that aloe-emodin may inhibit S phase progression. The cancer growth inhibition by aloe-emodin was due to apoptosis. The authors suggest that aloe-emodin represents a novel antitumor chemotherapeutic drug. [46]

Maxey C. M. Chung and colleagues 2007 found that Aloe-emodin induced anticancer effects in HepG2 cells via multiple pathways by affecting different protein targets and was able to decrease cell migration via up-regulation of the metastasis inhibitor, nm23. [47]

Giorgio Palu and colleagues report that Here we show that aloe-emodin selectively inhibits human neuroectodermal tumor cell growth in tissue cultures and in animal models. Neuroblastoma, pPNET, and Ewing's sarcoma cells were found highly susceptible to aloe-emotin, The authors write, however, that human malignant cells from epithelial and blood-derived tumors, as well as human hemopoietic progenitors and normal fibroblasts, were not sensitive to this compound. [48]

Toxicology [49]

Boudreau and Beland 2006 report that ingestion of Aloe vera is associated with diarrhea, electrolyte imbalance, kidney dysfunction, and conventional drug interactions; and contact dermatitis, erythema, and phototoxicity with topical applications. The authors reviewed the botany, physical and chemical properties, and biological activities of the Aloe vera plant. The toxic effects are related to aloin.

Alantoin in aloe latex, exudate from outer skin of aloe

It is used in beverages because of its taste and laxative effects.
The EU directive 88/388 sets maximum limits of 0,1 mg/kg in foods and beverages, and 50 mg/kg in alcoholic beverages. Incomplete separation of the leaf skin may cause aloin or other hydroxyanthracene derivatives to be present in Aloe vera gel. [50]

Aloe vera and diabetes [51]

According to Vogler and Ernst 1999 the clinical effectiveness of oral or topical aloe vera as adjunct for lowering blood glucose in diabetic patients as well as for reducing blood lipid levels in patients with hyperlipidaemia is not sufficiently defined at present. Aloe vera leaf pulp extract devoid of the gel has hypoglycaemic effect non-insulin dependent diabetes mellitus.

Okyar and colleagues 2001 report that Aloe vera leaf pulp extract showed hypoglycaemic activity on type 1 diabetic and type 2 diabetic rats. However, Aloe vera leaf gel extract showed hyperglycaemic activity on type 2 diabetic rats. The authors concluded that the pulps of Aloe vera leaves devoid of the gel could be useful in the treatment of type 2 diabetes. [52]

Tanaka and colleagues 2006 evaluated the anti-hyperglycemic effect of Aloe vera gel in mice. The authors isolated a five active compounds from lophenol, cycloartanol and their derivates. There were no differences between the five phytosterols, which reduced fasting blood glucose levels up to 64% compared with the control group. They concluded that Aloe vera gel and phytosterols derived from Aloe vera gel could be useful for the treatment of type 2 diabetes mellitus. [53]

Beppu and colleagues 2006 performed experimental trials to determine antidiabetic effects of Aloe vera. The authors found that The dietary administration of 10 KDa fraction powder to mice exerted an antioxidant activity in the pancreas and blood, which could protect islets of Langerhans from destruction. They also stress that the 10 KDa fraction powder alleviates the burden of insulin secretion as it has an inhibitory action on glucose absorption in the jejunum of rats. [54]

Perez and colleagues 2007 report that Aloe vera gel could be effective for the control of insulin resistance, which precedes type 2 diabetes mellitus. [55]

Analysis of components of Aloe vera [56]

According to A.Bozi and coleagues 2007 glucose, malic acid, and the polysaccharide acemannan, are the three main natural components of aloe vera gel. Maltodextrin remains a common adulterant of aloe vera gel powders.

Organic acid analysis to assess freshness of Aloe vera products

The authors found that lactic acid is a negative quality characteristic of aloe raw materials, indicating improper processing or incorrect storage. Fumaric acid, succinic acid, and pyruvates may be produced by enzymes. During fermentation and enzymatic degradation acemannan is degraded to acetic acid. Malic acid is the only organic acid contained in fresh aloe vera gel. Commercial aloe gel powders have citric and added for preservation and flavour.

Sugars

Acemanan in aloe vera gel powders should be the major polysaccharide. Bozi and colleagues measured the amount of mannose after acid hydrolysis gave a direct and rapid measurement acemannan in the gel powder.

Ginseng extract

A new ginseng extract called Cold-fx was developed by a spin-off company of the University of Alberta, CV Technologies. I contains 80 per cent poly-furanosyl-pyranosyl-saccharides and 10 percent protein from the ginseng roots.

The North American ginseng (Panax quiquefolium) is used as raw material. A publication of the Canadian Medical Association Journal (173, issue 9) claims that the extract is a safe,effective prophylactic treatment for upper respiratory tract infections.

It may boost production of natural killer cell activity, thought to decrease susceptibility to frequent colds. Further studies on its efficacy and safety to children and immunocompromised populations were recommended.

The composition of the Asian or Korean ginseng (Panax Ginseng C.A. Meyer) should also be analysed to find new ways to boost the human immune system to counter pandemics of influenza like an avian influenza outbreak.

Ronald Turner from the University of Virginia School of Medicine in the same journal warned of the many pitfalls faced by clinical studies of natural remedies for viral infections. Since the proposed mechanism of action of ginseng on colds is unclear, and the active compounds have not been identified, even though the extract was standardized " it is possible that there is lot-to-lot variability for important phytochemical components that are not measured". Peptides
Lactic acid bacteria
Isoprenoids
Lecithin
St. John's wort whose claim is emotional balance.
Dietary fibre as they prevent constipation.
Polyunsaturated fats to help to lower cholesterol
Carnitine[57]
Carnitine was discovered in 1905 and is also called vitamin BT. It is trimethylbetaine (beta-OH-gama-trimethylamino butyric acid). Long chain fatty acids are bind to carnitine which makes them able to cross the membrane of the mitochondrions and are there exposed to a beta-oxidation, it has a transmethylation and tyrosine effect. Carnitine has also a role in the oxidation but not in the transport of medium-chain fatty acids.[58]
Carnitine triggers the appetite and increases and bodyweight, the reason why it is being added to animal feed.


Biosynthesis of carnitine

The biosynthesis of carnitine which starts from lysine and methionine needs additional L-ascorbic acid and takes place in the liver. In case of an undersupply of vitamine C there will be very soon a drop of carnitine in the muscles resulting in weariness and weakness.[59]

Vitamine C is a cofactor of two dioxygenases reaction of the carnitine synthesis which needs also alpha-chetoglutarate. Guinea pigs with scurvy have low concentrations of carnitine in their blood. A low level of vitamine C reduces the availability of energy and the lipid metabolism due to a drop of carnitine.


Food as source of carnitine

Parallel to biosynthesis of carnitine in the liver food acts as an additional source. Vegetarians have a daily intake of 2 mg carnitine and mixed food bring 32 mg daily intake.


Food Carnitine
  mg in 100g
mutton 210
beef 70
pork 30
tomato 2.9
pear 2.7
pea 1.2
potato 0
carrot 0


Fifteen days of parenteral feeding leads to a drop of carnitine which cannot be compensated by biosynthesis. A carnitine substitution of 10 mg/day normalizes the concentration of carnitine in the serum and the beta-oxidation of long-chain fatty acids. Hemodialysis drops carnitine about 50%. Feeding carnitine reduces the amount of free fatty acids in the serum as it is forwarded to the beta-oxidation.

Hepatocirrhosis low carnitine is due to a diminished biosynthesis and reduced intake of food.


Carnitine and sport

Carnitine is being used as supplement in the nutrition of athletes to increase performance. A positive effect has not been confirmed.[60] It is considered as a non drug-doping substance but it is not on the "red list".
Folate
Psyllium to help to reduce cholesterol levels
Magnesium

Functional foods should taste good, be well prepared, and offer real benefits such as gastrointestinal function, antioxidant activity, micronutrients, positive activity on fetal and early life development.
On global market the functional foods will be sold under "Hard claims" [61] which are claims related to activities against diseases. " Soft claims " are used to describe preventive health claims.

Food supplements

Food supplements are defined in a leaflet of the German Institute for consumer Health and Veterinary Medicine (Bundesinstitut für Gesundheitlichen Verbraucherschutz und Veterinärmedizin (BgVV)
Food supplements are foods having one or more nutritional substances in concentrated form (mainly vitamins, minerals and trace elements), presenting a for food unusual form (pills or capsules etc.) Food supplements should be labeled as "Food supplement" together with the suggested daily intake.Food supplements are ruled by Food laws, in Germany by the LMBG ( Lebensmittel- und Bedarfsgegenständegesetz. they do not need a special release. Exception are dietary supplements , they do need a registration and a release.


Definition of Dietary Supplements according FDA

http://vm.cfsan.fda.gov/list.html.
Dietary supplement is any product taken by mouth, that contains a so called dietary ingredientänd its label states that it is a dietary supplement. Dietary supplements may be presented in form of pills, tablets, capsules, liquids or powders.


Definition of Dietary Ingredients

Dietary ingredients are present in dietary supplements. They may include vitamins,minerals, herbs, and aminoacids as well as substances such as enzymes, organ tissues, metabolites extracts or concentrates. The producer of food supplements is responsible for health safety of his products. He has to avoid deceiving informations and disease related statements ( 17 and 18 LMBG).
Substances with pharmacological activities are not food supplements. They are ruled under pharmacy laws.

The BgVV says that well-balanced adequate nutrition is sufficient to feed the daily nutrients.An increase of wellness through food supplements is according to BgVV doubtful. An exception is iodine and folic acid.For these two elements there is an undersupply in Germany. It is therefore advisable to use iodine salt in kitchen, community provisioning, production of bread, backery products and meat derivates.


Folic acid

Is important in the prevention of neural tube defects in the early pregnancy and reduces plasma homocystein which can lead to atherosclerotic damage.


Cancer, the medicine flop, a statement of Dr. Lothar Weissbach,president of the German Cancer Society

Dr. med. Lothar Weissbach is president of the German Cancer Society. He is an authority in research and treatment of human cancer. He works in the "Krankenhaus am Urban" Berlin.

In an interview with Hans Halter published in"Der Spiegel"[62] made the following statement:

"Early identification of cancer is very expensive, but not very effective.The interactive work between different specialists doctors is unsufficient and reduces the chances of the patients. The genetherapy will come but it will be necessary that more patients are willing to participate in clinical studies.Experts await the begin of the genetherapy for 2.003 or 2005.
One hundred years ago there were 43.000 death per year in Germany, on end of 1999 there were 218.000 death of the same cause. This come from a growing age of the population. Cancer is a disease of high age (this is not correct in related to breast and lung cancer, see WHO statistics:-comment of OurFood.com-). Pancreas cancer und lung cancer cannot be treated. Prognosis is bad. It is true that in ten years cancer will be at place number one in the death causes in Germany. We are not prepared for this.
Main concern are death cases from lung cancer, bowel cancer and breast cancer which has increased about 20% after introduction of early detection checks.

We have to learn that we can cure only a small part of cancer diseases. The knowledge gets through that we have to detect cancer earlier and -better as that- we have to avoid cancer."
Better understanding of food physiology, better care of our environment and self discipline regarding smoking and alcohol consume can be a precious contribution to reduce risk of cancer.


Breast cancer and high fat diet

High fat diet may increase breast cancer risc according to the London School of Hygiene and Tropical Medicine. The fat is not causal agent but instead causes depletion of an undiscovered essential agent that is normaly protective against breast cancer
Omportant factors engaged in the origine of breast cancer are:
1.- Deficiency, inadequate intake or depletion via a high fat diet.
2 - Age
3.-Estrogen.

Supplemented Foods


Isoflavonoids

: Isoflavonoids are phytochemicals which are free radical scavangers and can be extracted from soy beans.
Supplementing foods with isoflavonoids can help to reinforce the positive action of nature.

Flavonoids, such as isoflavones, anthocyanidins and flavonols

Phytoestrogens are substances which are estrogen-like. They are sometimes called endocrine disrupters. Some hypothesis say that exogenous substances with estrogenic or otherhormonally active properties may adversely affect human health.[63]

Endocrine disruptors can be industrial contaminants, such as pesticides and plasticizers, and others are natural phytoestrogens found in plants such as soy and in herbal supplements.

They may cause male wild-life animals in water contaminated by detergent, polychlorinated biphenyls (PCBs) and herbicide to express female characteristics and other modifications. Human development can also be feminized by exposure to estrogenic chemicals, affect breast growth and lactation, and could have a role in uterine diseases such as fibroids and endometriosis.

Endocrine-disrupting chemicals mostly exhibit estrogenic effects, but a few are anti-estrogenic or anti-androgenic,resulting in reduced fertility in breeding cattle. [64]
They are found in plants. Important phytoestrogens are ligans, isoflavones and coumetans.

Effect of phytoestrogens such as lignans on cancer risk

Lignans

They are found in flax seed (300 mg/100g), sesame seed (290 mg/100g), brassica vegetables (0,2-2 mg/100 g), red wine (0,09 mg/100 g).

Several hundred individual lignans have been discovered. Research, however, is focussed on lignans from flaxseed (Linum usitatissimum) and only few studies were made on lignans from Norwegian spruce bark (Picea abies).

When part of the human diet, some lignans are metabolised to form mammalian lignans known as enterediol and enterolactone by intestinal bacteria. Lignans that can be metabolised to form mammalian lignans are pinoresinol, lariciresinol, secoisolariciresinol, matairesinol, hydroxymatairesinol, syringaresinol and sesamin. [65]

Phytoestrogens may play a role in hormone-related diseases such as cancer, but epidemiological and clinical data are conflicting.

The mammalian lignans enterolactone and enterodiol are produced by the microflora in the colon of humans and animals from precursors in foods such as lignans. They have been suggested to have potential anticancer effects.

Lilian U. Thompson and colleagues in 2005 determined the production of mammalian lignans from precursors in food bars containing unground whole flaxseed and sesame seed. The authors demonstrated that precursors from unground whole flaxseed and sesame seed are converted by the bacterial flora in the colon to mammalian lignans. [66]

Sesame seed is not protective and negatively interferes with tamoxifen in inducing regression of established MCF-7 tumor size [67]

Flaxseed enhances the tumor growth-inhibitory effect of tamoxifen, but sesame seed was found by Sandra M.Sacco and colleagues to have no effect on tumor and tend to negate the tumor-inhibitory effect of tamoxifen, reducing apoptosis. The authors concluded in a 2008 study that sesame seed is not protective and negatively interferes with tamoxifen in inducing regression of established MCF-7 tumor size.

The Waagening lignan study January 2008: Enteroligans do not protect against colorectal cancer [68]

Peter C.H. Hollaman and colleagues say that high plasma enterodiol or enterolactone concentrations do not reduce risk of colorectal cancer. Enterolignans are biphenolic compounds that possess several biologic activities whereby they may influence carcinogenesis.

Enterodiol and enterolactone are a product of the activity of the microflora of the colon metabolising lignans from plants such as flax seed, whole grain cereals, berries, vegetables and fruits. The authors stressed that plasma enterodiol and colorectal increased the risk of colorectal cancer among current smokers.
The results contradict the study published in 2006.


The Waagening lignan study June 2006: Enteroligans protect against colorectal cancer [69]

Peter C.H. Hollaman and colleagues reported in June 2006 a substantial reduction in colorectal adenoma risk among subjects with high plasma concentrations of enterolignans, in particular, enterodiol. The authors write that findings could be important in the prevention of colorectal adenomas.

Enterolactone reduces the proliferation of prostate cancer cells in vitro [70]

According to Marc J. McCann and colleagues 2008 ecological data suggest that a long-term diet high in plant material rich in biologically active compounds, such as the lignans, can significantly influence the development of prostate cancer. The authors performed an in vitro study which suggests that the antiproliferative activity of enterolactone of the LNCaP human prostate cancer cell line in vitro is a consequence of altered expression of cell cycle associated genes. According to the authors this study provides evidence for the antiproliferative properties of a pure lignan in prostate cancer.

Dietary flaxseed reduces tumor growth in patients with breast cancer [71]

Lilian U. Thompson and colleagues found in 2005 that dietary flaxseed, the richest source of mammalian lignan precursors, increased the apoptosis of cancer cells, increased urinary lignan excretion and reduced tumor biological markers in postmenopausal patients with newly diagnosed breast cancer.

The authors concluded that dietary flaxseed has the potential to reduce tumor growth in patients with breast cancer.

Flaxseed, soy protein isolates and their action on breast cancer cells [72]

Previous study of Lilian U. Thompson and colleagues had found that flaxseed (FS) reduced while soy protein isolate (SPI) stimulated MCF-7 breast tumor growth in ovariectomized mice. In 2007 the authors found that combining SPI and FS resulted in a negation of SPI-induced tumor growth. Uterus weight was significantly increased by the SPI + FS group, while SPI alone induced an intermediate effect.

The authors concluded that although the SPI + FS and SPI groups exerted stimulatory effects on uterus weight, other histological parameters need to be measured to determine the overall safety of these breast cancer treatments on the uterus.

Flaxseed and soy protein isolates and their effect on breast cancer [73]

In several epidemiological studies, a phytoestrogen-rich diet containing lignans and isoflavones is associated with reduced breast cancer risk, but experimental findings are controversial.

In 2006 Lilian U. Thompson and colleagues found that in mouse, ligans of flaxseed reduced breast cancer growth, while isoflavones from soy protein enhanced it. The combination of soy protein with flaxseed reduced the tumor growth.

The authors concluded that dietary flaxseed did not stimulate the growth of estrogen responsive MCF-7 cancers in mice, while long-term consumption of soy protein did, and flaxseed reduced the tumor growth stimulating effect of soy protein. Flaxseed is therefore being suggested to attenuate tumor growth.

The combination of flaxseed with soy reduce the growth stimulatory effect on established breast cancer [74]

Concern over the safety of soy and its isoflavones are growing. Soy genistein was found to increase the risk of postmenopausal breast cancer. According to Lilian U. Thompson and colleagues in july 2007 wrote that flaxseed with enterodiol and enterolactone, was found to negate the tumor stimulatory effects of soy protein or genistein alone.

The authors, analysing the findings of their study, concluded that soy should be consumed together with lignan-rich foods to avoid an increased risk of postmenopausal breast cancer.

Isoflavones

Isoflavones are polyphenolic compounds produced almost exclusively by the members of the Fabaceae/ Leguminosae (bean) family. Important isoflavones are genistein, daidzein, glycitein and formononetin. Soy products contain the highest amounts of isoflavone, followed by legumes, meat products and other processed foods, cereals and breads, nuts and oilseeds, vegetables, alcoholic beverages, fruits, and non alcoholic beverages. [75]

Coumetans

A known coumestan is the coumestrol. Coumestans are estrogen-like substances (phytoestrogens) made by some plants. Coumestans may have anticancer effects according to the U.S. National Cancer Institute.

A new coumestan, tephcalostan has been isolated from the whole plant of Tephrosia calophylla BEDD. together with two known flavonoids. [76]

Flavonoids, lignans and reduction of risk of breath cancer [77]

Bryan Fink and colleagues investigated the association of dietary flavonoid intake with reduced risk of breast cancer in a population-based sample of US women. The authors found a decrease in breast cancer risk associated with flavonoid intake, most pronounced for flavonols, flavones, flavan-3-ols, and lignans in postmenopausal women.

The authors conclude that women consuming sufficient levels of flavonoids may benefit from their potential chemopreventive effects. Flavonoids antioxidants may thus reduce mortality among postmenopausal in breast cancer patients [78]

Brian Fink from the University of North Carolina states, write in another publication, that his team found that the breath-cancer mortality in postmenopausal women may be reduced in association with high levels of dietary flavones and isoflavones. No reduction of risk was found in premenopausal women.

Flavonoids and flavanones reduce oral and paryngeal cancer [79]

Rossi and colleagues 2007 in a study found that the intake of flavonoids was inversely related to the risk of various common neoplasms, but scanty data exist on oral and pharyngeal cancer. The authors applied data on food and beverage content of six major classes of flavonoids, for flavanones, for flavonols, and for total flavonoids. In this study no significant association emerged for isoflavones, anthocyanidins, flavan-3-ols, and flavones. The inverse relations with total flavonoids and flavanones was significant, whereas that with flavonols were nonsignificant.


Health benefits of flavonoids from citrus fruits

Enzymatic modification of the citrus flavonoid hesperidin improves bioavailability in humans [80]

Hesperidin is the predominant polyphenol from citrus fruits and juices, but it has reduced bioavailability due to the rutinoside moiety attached to the flavonoid.

In a study by Nielsen and colleagues 2006 the rhamnose group was removed to yield the corresponding flavonoid glucoside improving the bioavailability of the aglycone hesperetin.

The authors concluded that the bioavailability of hesperidin was modulated by enzymatic conversion to hesperetin-7-glucoside, thus changing the absorption site from the colon to the small intestine.


Hesperidin and naringin from orange and grape fruits can lead to reductions in cholesterol levels in lab animals [81]

Shela Gorinstein and colleagues 2007 compared the influence of hesperidin and naringin, the main flavonones of plasma antioxidant activity increasing flavonones.


Flavanones from citrus fruits may help to treat neurovegetative diseases [82]

According to Sam-Long Hwang and Gow-Chin Yen 2007 the citrus flavanones hesperidin, hesperetin, and neohesperidin from cirus fruits, have neuroprotective effects against H2O2-induced cytotoxicity in PC12 cells. The flavanones protect against oxidative stress, playing thus a neuroprotective role. Citrusfruits fruits have potential as functional foods for neuroprotectione.

The authors suggest the use of these flavanones in the intervention for neurodegenerative diseases such as Alzheimer's disease,

Soy as supplement in infant formulas

Soy as a supplement or replacement for maternal breast milk or cow's milk in infant formulas is becoming increasingly important. Antioxidant effects of isoflavones from soy, such as genistein, daidzein, and glycitein had been seen as some of good merits of soy.

However, according to ongoing discussions phytoestrogens in soy infant formulas may have an adversely affect human growth, development, or reproduction.

Genistein beside its antioxidant effect is also a phytoestrogen which may be hazardous to human development or reproduction. Concerns about oestrogen effects of genistein in human body are being discussed. [83]

A summary of the bibliography related to soy and Genistein in the management of menopause-related symptoms is given by Nelson HD. [84].

The outcomes of a discussion, leaded by US Center for the Evaluation of Risks to Human Reproduction (CERHR) of the National Institute of Environmental Health Services (NIEHS) and National Toxicology Program in March 2006, were:

When given orally, there was no threat from the reproductive and developmental effects of soy, supporting the safety of soy isoflavone dietary supplements. The effects of genistein in relation to heart disease or cancer risk, were not explored by the panelists.

One member of the pannel, however called for greater caution on this matter.

Soy Isoflavones are known for acting similarly to natural estrogens as well as performing protective functions within our bodies. When estrogen levels are low, Isoflavones and other phyto-estrogens bring the body to state of equilibrium. This balanced state reduces the effect of estrogen on our bodies' cells and therefore reduces the risk of estrogen linked cancers.

Long exposure to soy diet may reduce male fertility [85]

Nef and colleagues 2010 assessed the effects of isoflavone phytoestrogens in soybean effects on the development and function of the male reproductive system. Feeding soy-rich diet to mice the authors found that behaviour and fertility of adult mice were normal, however, sperm counts were 25 per cent lower, and 21 per cent smaller litter sizes, than found in mice fed a soy-free diet. Also reduced transcripts coding for androgen-response genes in Sertoli cells and Gapd-s, involved in sperm glycolysis and mobility were noted. The authors concluded that dietary soy may decrease male fertility.

Soy-based formula infant feeding should be avoided [86]

In a review 2009 Nef and collegues write that some indications that phyto-oestrogens, alone or in combination with other endocrine disruptors, may alter reproductive hormones, spermatogenesis, sperm capacitation and fertility. The authors call for more studies suggest perinatal phyto-oestrogen exposure to be reconsidered, in especial infants feeding on soy-based formula should be avoided. The authors in another review of 2009 acknowledge that phytoestrogens of soy favourably alter glycemic control, improve weight and fat loss, lower triglycerides, low density lipoprotein (LDL) cholesterol and total cholesterol, however, more studies are needed to identify which soy component is responsible for specific effects, which are the mechanisms engaged, and what are possible negative effects of the phytoestrogens of soy. [87]

Soy phytoestrogen present no apparent estrogenic effects [88]

In this study the risks of phytoestrogens as potential endocrine-disrupting chemicals (EDC) were compared with those posed by estradiol and other EDC. Kwack and colleagues 2009 estimated the soy products intake of Koreans to be 135.2 g/d which is an equivalent of 0.51 mg/kg body weight (bw)/d of phytoestrogens and compared it with Amercan diet low in soy products.

Estimated daily intakes (EDI) and estrogenic potencies (EP) the margins of safety (MOS) were used. Estradiol presents an MOS value of 0.05 for estradiol (MOS value <1, considered to exert a positive estrogenic effect); thus, MOS values of 1.89 for Japanese, 1.96 for Koreans, and 5.55 for Americans. The authors concluded that consumption of soybean-based foods exerted no apparent estrogenic effects, as all MOS values were all higher than 1, but poses a relatively higher health risk for humans than synthetic EDC such as dieldrin 27, nonylphenol 250, butyl benzyl phthalate 321, bisphenol A 1000, biochanin A 2203, and coumesterol 2898.

Functions of Genistein

Genistein as antioxidant reduces the risk for arteriosclerosis minimizing peroxidation and prevets thus LDL cholesterol being absorbed by aarterial walls.

Genistein blocks the enzime tyrosinereducing the risk of cancer. Breat and prostata cancer are also being said to be reduced by genistein.

Functions of daidzein

Daidzein has little estrogen activity but is very effective as antioxidant. It was linked to reduction of risk of mammary tumors and reduction of risk of osteoporosis.

Functions of glycitein

Glycitein has the greatest estrogenic activity levels of all the Isoflavones when measured in vivo. It is the most easily absorbed Isoflavone.

Special purpose value added soybeans

[89] Scientists are searching the loci controlling the accumulation of specific soybean isoflavones.

Reducing unwanted isoflavones while enhancing beneficial isoflavones could be a key-breeding target. Manipulation of isoflavone contents and profiles will result in the creation of special purpose value added soybeans.

Future research needs to focus on the production of a cultivar that consistently produces 5-6 mg/g of total isoflavone, with a white hilum and non-GMO herbicide resistance for the international soy protein isolate market.

Beneficial health claims for soy [90]

Phytoestrogen supplements have become popular as alternatives for hormone replacement therapy based on their potential as prevention of hormonedependent diseases. Isoflavonoids found in legumes, such as soybeans, are converted by intestinal bacteria to metabolites with increased or decreased estrogenic activity.

Microbial biotransformation plays a central role in regulating the biological activity of isoflavonoid phytoestrogens. They can convert them to potent estrogens or break them to nonestrogenic metabolites.

Microbial activities are also involved in prolonging enterohepatic circulation of isoflavonoids by decongugation of the liver isoflavonoid metabolites.

These activities result in delay in excretion, consequently prolonging the period of exposure of target tissues, such as reproductive organs. Detection of the specific bacteria from the human intestinal tract that are involved in the metabolism of phytoestrogens has been the subject of this study.

Specific bacteria involved in biotransformation of three natural isoflavonoids, biochanin A, formononetin and glycitein, to their primary more estrogenic metabolites (genistein, daidzein, and 6,7,4'-trihydroxyisoflavone) by demethylation, which also enhances their absorption, have been found.
One of the reasons for the lack of beneficial effect of phytoestrogens has been their conversion by bacteria to nonestrogenic metabolites.

FDA has granted the petition for a claim that the use of soy protein is safe, however, it still does not have a ruling on isoflavonoids for consumers. In addition to advancing the study of phytoestrogen metabolism, the data obtained provide background information that FDA can use when evaluating data on the beneficial or detrimental effects of phytoestrogens for regulatory purposes.


Catechin in chocolate

Catechin


Pine bark

Pine bark of Finland is according to the producer of Vitabak rich on bioflavonids. The content of bioflavonids of the bark rises as one gets in north direction.

Composition of 1 g bark
Flavonoids 33,4 mg
Calcium 680 mg
Iron 270 mg
Magnesium 250 mg
Zinc 89 mg
and 61% of fibres.

The University of Kuopio has started a research about LDL-Cholesterol reducing properties of Vitabark.
14 g of bark powder were given daily in form of bread to a special group. After one week blood cholesterol lowered about 17%.
Many bioflavonoids have a very bitter taste and are therefore generaly taken as supplements in time-release tablets or in capsules that will not dissolve radily in mouth.
Bioflavonoids are water-soluble substances associated with materials that often appear in fruits and vegetables as companions to vitamin C.According to Dr. Z. Zloch of Charles University in Czechoslovakia the antioxidant activity of bioflavonoids seems to result from their unique chemical structure; they act as reducing agents which are transported to the site where vitamin C is to be stored in the cell.
There is an increased uptake of vitamin C into the liver, kidney and adrenal gland when bioflavonoids were administrated with vitamin C. There is also an increased protection of the vitamin C against oxidation because the bioflavonoids convert the ascorbic acid to a less active form as dehydroascorbate.
Decrease in blood cholesterol in animals treated with vitamin C together with bioflavonoids was also noted by Dr. Zloch. The decrease was not so high when vitamin C was used without bioflavonoids[91].

Maritime pine

The Maritime Pine, Pinus pinaster, is a pine native to the western Mediterranean region. Often the old generic name Pinus maritima is used for the French maritime pine. Both names refer to the same tree. The bark is a source of proanthocyanidins, also known as procyanidin oligomeric proanthocyanidin (OPC), pycnogenol, leukocyanidin and leucoanthocyanin, they are flavanols.

Bibliography

1
Burri L, Hoem N, Banni S, and Berge K.
Marine omega-3 phospholipids: Metabolism and biological activities.
Int J Mol Sci, 13(11):15401-19, 11 2012.
http://www.mdpi.com/1422-0067/13/11/15401/pdf.

2
Schuchardt JP, Schneider I, Meyer H, Neubronner J, von Schacky C, and Hahn A.
Incorporation of epa and dha into plasma phospholipids in response to different omega-3 fatty acid formulations-a comparative bioavailability study of fish oil vs. krill oil.
Lipids Health Dis, 10:145, 8 2011.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3168413/.

3
Ulven SM, Kirkhus B, Lamglait A, Basu S, Elind E, Haider T, Berge K, Vik H, and Pedersen JI.
Metabolic effects of krill oil are essentially similar to those of fish oil but at lower dose of epa and dha, in healthy volunteers.
Lipids, 46(1):37-46, 1 2011.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3024511/.

4
Roberfroid, Marcel B.: Functional Foods; Ingredients Health and Nutrition; January 1999.

5
Kneucker,Dieter: Gesund essen mit Functional FoodLabor Praxis Nr.1; Januar 1999; 23.Jahrgang; S.4.

6
Guidance on the scientific requirements for health claims related to antioxidants, oxidative damage and cardiovascular health efsa panel on dietetic products, nutrition and allergies (nda).
http://www.efsa.europa.eu/en/efsajournal/doc/2474.pdf.

7
http://www.ffnmag.com/asp/articleDisplay.asp?strArticleId=530&strSite=FFNSite.
Kaori Nakajima: Japan's long, tough road to health claims regulations; Fuctional foods and Nutracuticals, August 2004.

8
http://www.ncbi.nlm.nih.gov/pubmed/18598379.
Morrow, L.E.; Kollef, M.H.: Probiotics in the intensive care unit: why controversies and confusion abound. Crit Care. 2008;12(3):160. Epub 2008 Jun 24.

9
http://www.spiegel.de/wirtschaft/0,1518,druck-597184,00.html.
Amann, Susanne: Marketing-Erfolg. Mit Joghurt Millionen scheffeln. Spiegel Online 22.12.2008.

10
http://www.danone.com/en/brands/business/fresh-dairy-products.html.
Danone: Healthy growth boosts flagship products.

11
http://www.ncbi.nlm.nih.gov/pubmed/17337434.
Khan SH, Ansari FA.: Probiotics-the friendly bacteria with market potential in global market. Pak J Pharm Sci. 2007 Jan;20(1):76-82.

12
http://www.ft.com/cms/s/0/7faa94c8-f193-11dd-8790-0000779fd2ac.html.
UK Financial Times: Taste for Danone's Essensis yoghurt dwindles. By Jenny Wiggins in London. February 3 2009 02:00.

13
http://www.fitsugar.com/129566.
FitSugar: Essensis: Healthy From the Inside Out. 02.07.2007.

14
http://www.soya.be/adez.php.
Soya, Information about Soy and Soya products.: AdeZ Fruit Juice and Soya.

15
http://www.thecoca-colacompany.com/presscenter/nr_20061011_americas_enviga.html.
New Enviga and Trade; Proven to burn Calories: Sparkling Green Tea Creates a Brand New Category That Combines Great Taste and Negative Calories.

16
http://www.cspinet.org/new/200702121.html.
CSPI: Enviga Study Casts Doubt on Calorie Burning & Weight-Loss Claims. Companies' Own Study Shows Many People May Expend Less Energy-Not More-After Drinking New Beverage. 12 February 2007.

17
Hap S and Gutierrez NA.
Functional properties of some new zealand fruit extracts towards selected probiotic and pathogenic bacteria.
Benef Microbes, pages 1-10, 9 2012.
http://www.ncbi.nlm.nih.gov/pubmed/22968373.

18
Morton, j. 1987. feijoa. p. 367–370. in: Fruits of warm climates. julia f. morton, miami, fl. feijoa: Feijoa sellowiana berg.
http://www.hort.purdue.edu/newcrop/morton/feijoa.html.

19
Sharm A and Zhou W:.
A stability study of green tea catechins during the biscuit making process.
Food Chemistry, 126(2):568-573, 5 2011.
http://dx.doi.org/10.1016/j.foodchem.2010.11.044.

20
Verhoef SP, Meyer D, and Westerterp KR.
Effects of oligofructose on appetite profile, glucagon-like peptide 1 and peptide yy3-36 concentrations and energy intake.
Br J Nutr, pages 1-6, 6 2011.
http://www.ncbi.nlm.nih.gov/pubmed/21679485.

21
Cani PD, Joly E, Horsmans Y, and Delzenne NM.
Oligofructose promotes satiety in healthy human: a pilot study.
Eur J Clin Nutr, 60(5):567-72, 5 2006.
http://www.ncbi.nlm.nih.gov/pubmed/16340949.

22
Parnell JA and Reimer RA.
Weight loss during oligofructose supplementation is associated with decreased ghrelin and increased peptide yy in overweight and obese adults.
Am J Clin Nutr, 89(6):1751-9, 6 2009.
http://www.ajcn.org/content/89/6/1751.long.

23
Roberfroid MB.
Introducing inulin-type fructans.
Br J Nutr, 93(Supl 1):S13-25, 4 2005.
http://www.ncbi.nlm.nih.gov/pubmed/15877886.

24
Shepherd SJ and Gibson PR.
Fructose malabsorption and symptoms of irritable bowel syndrome: guidelines for effective dietary management.
Journal of the American Dietetic Association, 106(10):1631-9, 2006.
http://sacfs.asn.au/download/SueShepherd_sarticle.pdf.

25
Muir JG, Shepherd SJ, Rosella O, Rose R, Barrett JS, and Gibson PR.
Fructan and free fructose content of common australian vegetables and fruit.
J Agric Food Chem, 55(16):6619-27, 8 2007.
http://www.ncbi.nlm.nih.gov/pubmed/17625872.

26
Muir JG, Rose R, Rosella O, Liels K, Barrett JS, Shepherd SJ, and Gibson PR.
Measurement of short-chain carbohydrates in common australian vegetables and fruits by high-performance liquid chromatography (hplc).
J Agric Food Chem, 57(2):554-65, 1 2009.
http://www.ncbi.nlm.nih.gov/pubmed/19123815.

27
Biesiekierski JR, Rosella O, Rose R, Liels K, Barrett JS, Shepherd SJ, Gibson PR, and Muir JG.
Quantification of fructans, galacto-oligosacharides and other short-chain carbohydrates in processed grains and cereals.
J Hum Nutr Diet, 24(2):154-76, 4 2011.
http://www.ncbi.nlm.nih.gov/pubmed/21332832.

28
http://jama.ama-assn.org/cgi/external_ref?access_num=10.1016/S1470-2045(02)00777-5&link_type=DOI.
Phyto-oestrogens and cancer. Lancet Oncol. 2002; 3:364-373.

29
http://jama.ama-assn.org/cgi/ijlink?linkType=ABST&journalCode=jcem&resid=83/7/2223.
Tham DM, Gardner CD, Haskell WL. Clinical review 97: potential health benefits of dietary phytoestrogens: a review of the clinical, epidemiological and mechanistic evidence. J Clin Endocrinol Metab. 1998;83:2223-2235.

30
http://jama.ama-assn.org/cgi/external_ref?access_num=10.1016/S0163-7827(02)00006-1&link_type=DOI.
Moreau RA, Whitaker BD, Hicks KB. Phytosterols, phytostanols, and their conjugates in foods: structural diversity, quantitative analysis, and health-promoting uses. Prog Lipid Res. 2002;41:457-500.

31
Jefferson WN, Patisaul HB, and Williams C.
Reproductive consequences of developmental phytoestrogen exposure.
Reproduction, 1 2012.
http://www.ncbi.nlm.nih.gov/pubmed/22223686.

32
http://www.bfr.bund.de/cm/245/isolated_isoflavones_are_not_without_risk.pdf.
Federal Institute for Risk Assessment: Isolated isoflavones are not without risk. 29 October 2007.

33
http://pubs.acs.org/doi/full/10.1021/jf801344x?cookieSet=1.
Kuhnle, Gunter G. C.; Dell'Aquila, Caterina; Aspinall, Sue M.; Runswick, Shirley A.; Mulligan, Angela A.; Bingham, Sheila A.: Phytoestrogen Content of Foods of Animal Origin: Dairy Products, Eggs, Meat, Fish, and Seafood. J. Agric. Food Chem., 2008, 56 (21), pp 10099-10104. Publication Date (Web): October 16, 2008. Doi: 10.1021/jf801344x.

34
http://cebp.aacrjournals.org/cgi/content/full/14/1/213.
Low, Y.-L.; Taylor, J. I.; Grace, P. B.; Dowsett, M.; Scollen, S.; Dunning, A.M.; Mulligan, A.A.; Welch, A.A.; Luben, R.N.; Khaw, K.T.; Day, N.E.; Wareham, N.J.; Bingham, S.A. Phytoestrogen exposure correlation with plasma estradiol in postmenopausal women in European prospective investigation of cancer and nutrition-Norfolk may involve diet-gene interactions Cancer Epidemiol., Biomarkers Prev. 2005 14 1 213 220.

35
http://cebp.aacrjournals.org/cgi/content/full/16/5/1009.
Low, Y.L.; Dunning, A. M.; Dowsett, M.; Folkerd, E.; Doody, D.; Taylor, J.; Bhaniani, A.; Luben, R.; Khaw, K.T.; Wareham, N.J.; Bingham, S.A. Phytoestrogen exposure is associated with circulating sex hormone levels in postmenopausal women and interact with ESR1 and NR1I2 gene variants Cancer Epidemiol., Biomarkers Prev. 2007 16 5 1009 1016.

36
http://cancerres.aacrjournals.org/cgi/content/full/66/18/8980.
Low, Y.L.; Dunning, A. M.; Dowsett, M.; Luben, R.N.; Khaw, K.T.; Wareham, N.J.; Bingham, S.A. Implications of gene-environment interaction in studies of gene variants in breast cancer: An example of dietary isoflavones and the D356N polymorphism in the sex hormone-binding globulin gene Cancer Res. 2006 66 18 8980 8983.

37
http://humrep.oxfordjournals.org/cgi/content/full/21/5/1184.
Fraser, Lynn R.; Beyret, Ergin; Milligan, Stuart R.; Adeoya-Osiguwa, Susan A.: Effects of estrogenic xenobiotics on human and mouse spermatozoa. Human Reproduction 2006 21(5):1184-1193; doi:10.1093/humrep/dei486.

38
http://humrep.oxfordjournals.org/cgi/content/abstract/den243v1.
Jorge E. Chavarro, Thomas L. Toth , Sonita M. Sadio , and Russ Hauser. Soy food and isoflavone intake in relation to semen quality parameters among men from an infertility clinic. Human Reproduction, July 24, 2008 DOI: 10.1093/humrep/den243.

39
http://humrep.oxfordjournals.org/cgi/content/abstract/21/4/994.
Guarducci, Elena; Nuti, Francesca; Becherini, Lucia; Rotondi, Mario; Balercia, Giancarlo; Forti, Gianni; Krausz, Csilla: Estrogen receptor alpha promoter polymorphism: stronger estrogen action is coupled with lower sperm count. Human Reproduction 2006 21(4):994-1001; doi:10.1093/humrep/dei439.

40
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids==16414215.
Garrido A, De la Maza MP, Hirsch S, Valladares L: Soy isoflavones affect platelet thromboxane A2 receptor density but not plasma lipids in menopausal women. Elsevier Maturitas. 2006 Jun 20;54(3):270-6. Epub 2006 Jan 18.

41
http://jama.ama-assn.org/cgi/content/full/294/12/1493.
Schabath, Matthew, B.; Hernandez, Ladia M.; Wu, Xifeng; Pillow, Patricia C.; Spitz, Margaret R.: Dietary Phytoestrogens and Lung Cancer Risk JAMA.2005;294:No. 12, September 28, 2005. 1493-1504.

42
http://www.ncbi.nlm.nih.gov/pubmed/15531292.
Talmadge JE, Chavez J, Jacobs L, Munger C, Chinnah T, Williamson D, Yates K. 2004 Fractionation of Aloe vera L. inner gel, purification and molecular profiling of activity. IASC Aloe Special Issue. International Immunopharmacology. 14(4): 1757-1773.

43
http://www.ncbi.nlm.nih.gov/pubmed/17499928.
Maenthaisong R.; Chaiyakunapruk N.; Niruntraporn S.; Kongkaew C.: The efficacy of aloe vera used for burn wound healing: a systematic review. Burns. 2007 Sep;33(6):713-8. Epub 2007 May 17.

44
http://www.ncbi.nlm.nih.gov/pubmed/9776900.
Aterton, P.; Aloe vera: magic or medicine? Nurs Stand. 1998 Jul 1-7;12(41):49-52.

45
http://www.cancer.gov/templates/drugdictionary.aspx?expand=A.
National Cancer Institute: Dictionary of Cancer Terms: Aloe-emodin.

46
http://cat.inist.fr/?aModele=afficheN&cpsidt=16266603.
Mildred Acevedo-Duncan, Christopher Russell, Sapna Patel, Rekha Patel: Aloe-emodin modulates PKC isozymes, inhibits proliferantion, and induces apoptosis in U-373MG glioma cells. International Immunopharmacology Volume 4, Issue 14, (20 December 2004) Pages 1775-1784.

47
http://www3.interscience.wiley.com/journal/114182354/abstract?CRETRY=1&SRETRY=0.
Dong Lu, Guo; Shen, Han-Ming; Nam Ong, Choon; Chung, Maxey C. M.: Anticancer effects of aloe-emodin on HepG2 cells: Cellular and proteomic studies. Proteomics Clinical Applications: Volume 1 Issue 4. Pages 410-419 Published Online: 13 Mar 2007.

48
http://www.ge.infm.it/biofisica/Adobe/Diaspro/Aloe%20pecere00.PDF.
Teresa Pecere, M. Vittoria Gazzola, Carla Mucignat, Cristina Parolin, Francesca Dalla Vecchia, Andrea Cavaggioni, Giuseppe Basso, Alberto Diaspro, Benedetto Salvato, Modesto Carli, and Giorgio Palu: Aloe-emodin is a New Type of Anticancer Agent with Selective Activity against Neuroectodermal Tumors1.

49
http://www.ncbi.nlm.nih.gov/pubmed/16690538.
Boudreau MD, Beland FA: An evaluation of the biological and toxicological properties of Aloe barbadensis (miller), Aloe vera. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev, 2006 Apr;24(1):103-54.

50
http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CELEX:31988L0388:EN:HTML.
Council Directive 88/388/EEC of 22 June 1988 on the approximation of the laws of the Member States relating to flavourings for use in foodstuffs and to source materials for their production.

51
http://www.ncbi.nlm.nih.gov/pubmed/10885091.
Vogler BK, Ernst E. Aloe vera: a systematic review of its clinical effectiveness. Br J Gen Pract. 1999 Oct;49(447):823-8.

52
http://www.ncbi.nlm.nih.gov/pubmed/11268118.
Okyar, A.; Can, A.; Akey, N.; Baktir, G.; Sütlüplinar N.: Effect of Aloe vera leaves on blood glucose level in type I and type II diabetic rat models. Phytother Res. 2001 Mar;15(2):157-61.

53
http://www.ncbi.nlm.nih.gov/pubmed/16819181.
Tanaka M, Misawa E, Ito Y, Habara N, Nomaguchi K, Yamada M, Toida T, Hayasawa H, Takase M, Inagaki M, Higuchi R.: Identification of five phytosterols from Aloe vera gel as anti-diabetic compounds. Biol Pharm Bull. 2006 Jul;29(7):1418-22.

54
http://www.ncbi.nlm.nih.gov/pubmed/16406411.
Beppu H, Shimpo K, Chihara T, Kaneko T, Tamai I, Yamaji S, Ozaki S, Kuzuya H, Sonoda S. : Antidiabetic effects of dietary administration of Aloe arborescens Miller components on multiple low-dose streptozotocin-induced diabetes in mice: investigation on hypoglycemic action and systemic absorption dynamics of aloe components. J Ethnopharmacol. 2006 Feb 20;103(3):468-77. Epub 2006 Jan 6.

55
http://www.ncbi.nlm.nih.gov/pubmed/18186589.
Pérez YY, Jiménez-Ferrer E, Zamilpa A, Hernández-Valencia M, Alarcón-Aguilar FJ, Tortoriello J, Román-Ramos R.: Effect of a polyphenol-rich extract from Aloe vera gel on experimentally induced insulin resistance in mice. Am J Chin Med. 2007;35(6):1037-46.

56
http://www.aseanfood.info/Articles/11018276.pdf.
Bozzi, A.; Perrin, C.; Austin, S.; Arce Vera, F.: Quality and authenticity of commercial aloe vera gel powders. Food Chemistry. Volume 103,Issue 1, 2007, Pages 22-30. doi:10.1016/j.foodchem.2006.05.061.

57
Kasper, Heinrich: Ernährungsmedizin und Diätetik; Urban and Schwarzenberg 8. Auflage, 1996 Pg 20.

58
o.V.: A role of carnitine in medium-chain fatty acid metabolism? Nutr. Rev. 49 (1991) 243-245.

59
Biesalski, Hans-Konrad: Ernährungsmedizin Thieme, 1995 pg 130.

60
Scheck, A.: L-Carnitin: Sinn und Unsinn der Substituition einer körpereigenen Substanz.; Ernährungs-Umschau 41 (1994) 9 - 15.l.

61
Juretko, Axel: Facts über Functional Food Wissenschaftliche Informationstagung in Berlin; Lebensmitteltechnik 3/1999 S. 29.

62
Halter,Hans: Die ärzte haben versagt Der President der Deutschen Krebsgesellschaft Lothar Weissbach über die Mängel der Früherkennung, die Versäumnisse der Mediziner und die Zukunft der Tumortherapie; Der Spiegel 12/2000, page 230.

63
Juberg, Daland R.: An Evaluation of Endocrine Modulators: Implications for Human Health. Ecotoxicology and Environmental Safety. Volume 45, Issue 2, February 2000, Pages 93-105. Doi:10.1006/eesa.1999.1851.

64
McLachlan, John A.; Weatherhead, Erica Simpson; Melvenia Martin: Endocrine disrupters and female reproductive health. Best Practice & Research Clinical Endocrinology & Metabolism. Volume 20, issue1, March 2006, Pages 63-75. Doi: 10.1016/j.beem.2005.09.003.

65
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16898863.
Thompson LU, Boucher BA, Liu Z, Cotterchio M, Kreiger N. Phytoestrogen content of foods consumed in Canada, including isoflavones, lignans, and coumestan. Nutr Cancer 2006; (cited 2007 1 Mar);54(2):184-201.

66
http://www.informaworld.com/smpp/content?content=10.1207/s15327914nc5202_6.
Coulman, Karen D. Liu, Zhen; Hum, Winston Quan Michaelides, John; Thompson, Lilian U.: Whole sesame seed is as rich a source of mammalian lignan precursors as whole flaxseed. Nutr Cancer. 2005;52(2):156-65.

67
http://www.menopausejournal.com/pt/re/menopause/abstract.00042192-200815010-00029.htm;jsessionid=HcBZwK2SWyrzYSL0zzB2MvLF7XZVqJhrJLY33x7QS1jJnXhWldy5!1122534142!181195628!8091!-1.
Sacco, Sandra M.; Chen, Jianmin; Power, Krista A.; Ward, Wendy E.; Thompson, Lilian U.: Lignan-rich sesame seed negates the tumor-inhibitory effect of tamoxifen but maintains bone health in a postmenopausal athymic mouse model with estrogen-responsive breast tumors. Menopause. 2008 Jan-Feb;15(1):171-9.

68
http://aje.oxfordjournals.org/cgi/content/abstract/kwm349v1.
Kuijsten, Anneleen; Hollman, Peter C. H.; Boshuizen, Hendriek C.; Buijsman, Michel N. C. P.; van 't Veer, Pieter; Kok, Frans J.; Arts, Ilja C. W.; Bueno-de-Mesquita, H. Bas: Plasma Enterolignan Concentrations and Colorectal Cancer Risk in a Nested Case-Control Study. American Journal of Epidemiology. Published on-line ahead of print 12 January 2008, doi:10.1093/aje/kwm349.

69
http://cebp.aacrjournals.org/cgi/content/abstract/15/6/1132.
Kuijsten, Anneleen; Arts, Ilja C.W.; Hollman, Peter C.H.; van't Veer, Pieter; Kampman Ellen: Plasma Enterolignans Are Associated with Lower Colorectal Adenoma Risk. Cancer Epidemiol Biomarkers Prev 2006 15: 1132-1136 doi: 10.1158/1055-9965.EPI-05-0991.

70
http://www3.interscience.wiley.com/journal/117954792/abstract?CRETRY=1&SRETRY=0.
McCann, Mark J.; Gill, Chris I. R.; Linton, Trevor; Berrar, D.; McGlynn, Hugh; Rowland, Ian R.: Enterolactone restricts the proliferation of the LNCaP human prostate cancer cell line in vitro. Molecular Nutrition & Food Research Published online ahead of print, 8 April 2008, doi: 10.1002/mnfr.200700052.

71
http://clincancerres.aacrjournals.org/cgi/content/abstract/11/10/3828.
Thompson, Lilian U.; Chen, Jian Min; Li,; Strasser-Weippl, Kathrin; Goss, Paul E.: Dietary flaxseed alters tumor biological markers in postmenopausal breast cancer. Clin Cancer Res 2005 May 15;11(10):3828-35.

72
http://www.informaworld.com/smpp/content~content=a783547576~db=all~order=page.
Power, Krista A.; Ward, Wendy E.; Chen, Jian Min,; Saarinen, Niina M.; Thompson, Lilian U.: Flaxseed and soy protein isolate, alone and in combination, differ in their effect on bone mass, biomechanical strength, and uterus in ovariectomized nude mice with MCF-7 human breast tumor xenografts. J Toxicol Environ Health A. 2007 Nov;70(22):1888-96. DOI: 10.1080/15287390701549179.

73
http://www3.interscience.wiley.com/cgi-bin/abstract/112550811/ABSTRACT.
Saarinen, Niina M.; Power Krista; Chen, Jianmin; Thompson, Lilian U.: Flaxseed attenuates the tumor growth stimulating effect of soy protein in ovariectomized athymic mice with MCF-7 human breast cancer xenografts. Int J Cancer 2006 Aug 15;119(4):925-31.

74
http://www3.interscience.wiley.com/cgi-bin/abstract/114281170/ABSTRACT?CRETRY=1&SRETRY=0.
Power Krista A.; Thompson, Lilian U.: Can the combination of flaxseed and its lignans with soy and its isoflavones reduce the growth stimulatory effect of soy and its isoflavones on established breast cancer? Mol Nutr Food Res. 2007 Jul;51(7):845-56. Review. DOI: 10.1002/mnfr.200600218.

75
http://www.springerlink.com/content/c1wx00ufqkwl/?p=e92cfdd557f64fa18e33b29ba2eb81de&pi=77.
Horn-Ross, P.L.; Barnes, S.; Lee, M.; Coward, L.; Mandel, J.E.; Koo J.; John, E.M.; Smith, M.: Assessing phytoestrogen exposure in epidemiologic studies: development of a database (United States). Cancer Causes Control 2000 Apr;11(4):289-98.

76
http://www.jstage.jst.go.jp/article/cpb/51/2/51_194/_article/-char/en.
Pennaka Hari Kishore, Mopuru Vijaya Bhaskar Reddy, Duvvuru Gunasekar, Madugula Marthanda Murthy, Cristelle Caux and Bernard Bodo, A New Coumestan from Tephrosia calophylla, Chem. Pharm. Bull., Vol.51, 194-196 (2003). doi:10.1248/cpb.51.194.

77
http://aje.oxfordjournals.org/cgi/content/abstract/165/5/514.
Fink, Brian N.; Steck, Susan E.; Wolff, Mary S.; Britton, Julie A.; Kabat, Geoffrey C.; Schroeder, Jane C.; Teitelbaum, Susan L.; Neugut, Alfred I.; Gammon, Marilie D. : Dietary Flavonoid Intake and Breast Cancer Risk among Women on Long Island. Am. J. Epidemiol. March 2007 165: 514-523; doi:10.1093/aje/kwk033.

78
http://cebp.aacrjournals.org/cgi/content/abstract/16/11/2285.
Fink, B.N.; Steck, S.E.; Wolff, M.S.; Britton, J.A.; Kabat, G.C.; Gaudet, M.M.; Abrahamson, P.E.; Bell, P.; Schroeder, J.C.; Teitelbaum, S.L.; Neugut, A.I.; Gammon: M.D. Dietary Flavonoid Intake and Breast Cancer Survival among Women on Long Island. Cancer Epidemiology, Biomarkers & Prevention. November 2007, Volume 16, Number 11, Pages 2285-2292.

79
http://cebp.aacrjournals.org/cgi/content/abstract/16/8/1621.
Rossi,M.; Garavello, W.; Talamini, R.; Negri, E.; Bosetti, C.; Dal Maso, L.; Lagiou, P.; Tavani, A.; Polesel, J.; Barzan, L.: Flavonoids and the Risk of Oral and Pharyngeal Cancer: A Case-Control Study from Italy. Cancer Epidemiol. Biomarkers Prev., August 1, 2007; 16(8): 1621 - 1625.doi: 10.1158/1055-9965.EPI-07-0168.

80
http://jn.nutrition.org/cgi/content/abstract/136/2/404.
Nielsen, Inge Lise F.; Chee, Winnie S.S.; Poulsen, Lea; Offord-Cavin, Elizabeth; Rasmussen,Salka E.; Frederiksen, Hanne; Enslen, Marc ; Barron, Dennis; Horcajada, Marie-Noelle; Williamson, Gary: Bioavailability Is Improved by Enzymatic Modification of the Citrus Flavonoid Hesperidin in Humans: A Randomized, Double-Blind, Crossover Trial. J. Nutr. 2006 136: 404-408.

81
http://www3.interscience.wiley.com/cgi-bin/abstract/114178333/ABSTRACT?CRETRY=1&SRETRY=0.
Gorinstein, Shela; Leontowicz, Hanna; Leontowicz, Maria ; Krzeminski, Ryszard; Gralak, Mikolaj; Jastrzebski, Zenon; Park, Yong-Seo; Jung, Soon-Teck; Kang, Seong-Gook; Trakhtenberg Simon: Effect of hesperidin and naringin on the plasma lipid profile and plasma antioxidant activity in rats fed a cholesterol-containing diet. Journal of the Science of Food and Agriculture, Vol 87, issue 7. Pages 1257-1262. Published Online: 26 Mar 2007. doi: 10.1002/jsfa.2834.

82
http://pubs.acs.org/cgi-bin/abstract.cgi/jafcau/asap/abs/jf072826r.html.
Hwang, Sam-Long; Yen, Gow-Chin: Neuroprotective Effects of the Citrus Flavanones against H2O2-Induced Cytotoxicity in PC12 Cells. Journal of Agricultural and Food Chemistry. Published on-line ahead of print, doi: 10.1021/jf072826r Received September 23, 2007.

83
Farmakalidis E, Hathcock JN, Murphy PA. Oestrogenic potency of genistin and daidzin in mice. Food Chem Toxicol 1985 Aug;23(8):741-5.

84
Nelson HD, Haney E, Humphrey L, Miller J, Nedrow A, Nicolaidis C, Vesco K, Walker M, Bougatsos C, Nygren P. Management of Menopause-Related Symptoms. Evidence Report/Technology Assessment No. 120. (Prepared by the Oregon Evidence-based Practice Center, under Contract No. 290-02-0024.) AHRQ Publication No. 05-E016-2. Rockville, MD: Agency for Healthcare Research and Quality. March 2005.

85
http://www.ncbi.nlm.nih.gov/pubmed/20171261.
Cederroth CR, Zimmermann C, Beny JL, Schaad O, Combepine C, Descombes P, Doerge DR, Pralong FP, Vassalli JD, Nef S: Potential detrimental effects of a phytoestrogen-rich diet on male fertility in mice. Mol Cell Endocrinol. 2010 Feb 18.

86
http://www.ncbi.nlm.nih.gov/pubmed/19919579.
Cederroth CR, Auger J, Zimmermann C, Eustache F, Nef S: Soy, phyto-oestrogens and male reproductive function: a review Int J Androl. 2009 Nov 16.

87
http://www.ncbi.nlm.nih.gov/pubmed/19433245.
Cederroth CR, Nef S: Soy, phytoestrogens and metabolism: A review. Mol Cell Endocrinol. 2009 May 25;304(1-2):30-42.

88
http://www.ncbi.nlm.nih.gov/pubmed/20077194.
Kwack SJ, Kim KB, Kim HS, Yoon KS, Lee BM: Risk assessment of soybean-based phytoestrogens. J Toxicol Environ Health A. 2009;72(21-22):1254-61.

89
http://www.ahrq.gov/downloads/pub/evidence/pdf/menopause/menopaus.pdf.
K. Meksem, V. N Njiti, W. J Banz, M. J Iqbal, My. M Kassem, D. L Hyten, J. Yuang, T. A Winters, and D. A Lightfoot: Genomic regions that underlie soybean seed isoflavone content; J Biomed Biotechnol. 2001; 1(1): 38-44. doi: 10.11551/S1110724301000110.

90
http://www.fda.gov/nctr/science/05-06_Research_Plans/pdf/FY2005-2006ResDoc.pdf.
Rafii, Fatemeh:Importance of Human Intestinal Microflora in Conversion of Phytoestrogens to Estrogenic Compounds (E0700701); Fy 200y 2006 Researche Accoplishments and Plans, National Center for Toxicological Researche.

91
Zloch, Z. International J.Vit. Res. 39: 269 (1969).

See also: Related OurFood News
Copyright © 1998 - 2013 by K. H. Wilm - Impressum