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Subsections

Food Supplements

A food supplement is, typically, a nutrient added to a foodstuff which would otherwise not contain that nutrient. In general, the term is restricted to those additives which are deemed to be positive for health, growth or well-being. [1]

Food supplements are regulated in the EU by the Directive 2002/46/EC of the European Parliament of 10 June 2002 on the approximation of the laws of the Member States relating to food supplements.[2]

Medicinal products

Medicinal Products for human use are defined by Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use and are a distinct category of products separated from food supplements.

The food supplements directive states that there is an increasing number of products marketed in the Community as foods containing concentrated sources of nutrients and presented for supplementing the intake of those nutrients from the normal diet.

An adequate and varied diet could, under normal circumstances, provide all necessary nutrients for normal development and maintenance of a healthy life in quantities which meet those established and recommended by generally acceptable scientific data.

However, surveys show that this ideal situation is not being achieved for all nutrients and by all groups of the population across the Community.

Consumers, because of their particular lifestyles or for other reasons, may choose to supplement their intake of some nutrients through food supplements.


Antioxidants in dietary supplements

Many dietary supplements are labelled as antioxidants. The price vary from product to product. Sometimes it possible to bye a cheap products which have the same activities as expensive products. Co-enzyme Q10 can be added using sheep products.
Ingredient Oxano Anti-Age tetesept Multi - Raucher Recommended
per capsule     A-Z in one vitamine Vitamine for
  Health+ Merz Spencer Pharma Abtei***  
  Fitness   Food Aldenhoven    
             
Vitamin A µg 275,2 343,7 800 850 - Cell growth,skin
β -carotin mg - - 900 - - Vitamin A builder
Vitamin C mg 225 29,5 60 75 112,5 Bones,
            connective tissue
Vitamin E mg 36 152 10 12 18 Cell, metabolism
Vitamin B1mg - - 1,40 1,40 - Muscle,metabolism
Vitamin B2mg - - 1,60 1,70 2,6 Skin, metabolism
Vitamin B6mg - - 1,60 1,80 - proteins physiol
Vitamin B12µg - - 1,00 3,00 - Cell, metabolism
Vitamin D3µg - - 5,00 5,00 - Bones
Vitamin K1µg - - 80 - - Antihemorrhage
Pantothenic            
acid mg - - 6,00 6,00 - Skin, metabolism
Folic acid µg - - 200 150 - Cell
Niacinamide            
mg - - 18 18 - Cell energy
Biotin µg - - 150 100 - Skin, hair, nail
Calcium mg - 3 200 200 - Bone, tooth
Chloride mg - - 36,4 - -  
Chromium µg - - 60 - 60 Metabolism of
            carbohydrates
l-Cisteine mg - - 9 - -  
Iron mg - - 6 5 - Oxygen transport
Potassium mg - - 60 - -  
Copper mg - - 1 1 - Cell physiology
Magnesium mg - - 120 150 - Muscle
Manganese mg - - 1,2 1,0 - Cell physiology
Molybdenum µg - - 80 80 - Enzyme activity
Phosphorus mg - - 103 - -  
Selenium µg - - 25 30 - Cell activity
Silicon mg - - 2 - -  
Zinc mg 5 2,25 9,5 5 - Cell physiology
Iodine µg - - - 100 - Thyroid function
Fluoride µg - - - 250 - Dental enamel
Co-enzyme            
Q10 mg 10 0,25 - - - Cell physiology
Anthocyane*mg 50 - - - - Cell physiology
Bioflavonoids**            
mg - - 5 - 12 Cell physiology
Borage oil mg - 407 - - - Omega-6 acid
Linseed oil mg - 45 - - - Omega-3-acid
Price per            
capsule EUR 0.50 0.18 0.14 0.04 0.30  
             
Ingredient Oxano Anti-Age tetesept Multi - Raucher Recommendet
per capsule     A-Z in one vitamine Vitamine for
  Health+ Merz Spencer Pharma Abtei***  
  Fitness   Food Aldenhoven    
* from red grapes            
*** from citrus            
****Vitamines            
for smoker            


Food industry is challenged to produce food on basis of an "optimal nutrition" concept [3]

Food choice is increasingly being influenced by health issues, creating opportunities for new product development, say El and Simsek in a 2012 review. Food scientists call for "optimal nutrition" as the optimization of a daily nutrition model with nutrients and bioactive compounds to prevent diseases an promote healthy life.

Legal bases of health claims

The Food-Based Dietary Guidelines of the World Health Organization (WHO) 2003 should be the bases of all activities, such as the European Union (EU) legislation on health claims and compulsory nutrition facts label in many countries increase the consumer awareness of calories, content of fat, trans-fatty acids, carbohydrates and salt. Australia and New Zealand, Canada, EU, India, Mexico, United States and others already implemented the nutritional label on foods. The WHO dietary guidelines recommend the limitation of total fat intake <30%, saturated fats <10%, and simple carbohydrates <10% of total caloric intake. [4]

Similar data for healthy foods are supported by the 2010 Dietary Guidelines for Americans to promote health, reduce the risk of chronic diseases, and reduce the prevalence of overweight and obesity through improved nutrition and physical activity. [5]


Reducing energy density of foods

Reducing energy density of foods may be achieved by increasing water or air content, using intense sweeteners bulk agents, resistant starches, carbohydrate- and/or protein-based fat replacers. Other researches focus on energy reduction by the inhibition of enzymes in carbohydrate and/or fat digestion, but is limited to specific group of obese consumers.

Functional foods

Bioactive peptides are known to exert regulatory functions in humans. They are being isolated from milk, eggs, meat, marine organisms, soy, wheat, broccoli, and rice. Some bioactive compounds are used to enrich foods or as supplements. Most prominents are: Coenzyme Q10, L-carnitine, alpha-lipoic acid, lignan, isothiocyanates, curcumin, isoflavone, resveratrol, lycopene, beta-glucan, inulin, omega-3 fatty acids, sterol and stanol.

However, much still remains to be done. The authors call on the food industry to reduce the number of energy-dense products, to reduce salt, added sugar, trans-fatty acid, and saturated fat content in processed foods.

Food science and technology need to introduce these new food-based dietary guidelines focusing on food physics, food storage and preservation, nutrient restoration and fortification of foods, and the development of designer foods and functional foods.


WHO diet guidelines 2003 [4]

Ranges of population nutrient intake goals
Dietary factor Goal % of total energy
Total fat 15-30%
Saturated fatty acids <10%
Polyunsaturated fatty acids (PUFAs) 6-10%
n-6 Polyunsaturated fatty acids (PUFAs) 5-8%
n-3 Polyunsaturated fatty acids (PUFAs) 1-2%
Trans fatty acids <1%
Monounsaturated fatty acids (MUFAs) By difference (a)
Total carbohydrate 55-75% (b)
Free sugars <10% (c)
Protein 10-15% (d)
Cholesterol <300 mg per day
Sodium chloride (sodium) <5 g per day (<2 g per day) (e)
Fruits and vegetables 5400 g per day
Total dietary fibre From foods (f)
Non-starch polysaccharides (NSP) From foods (f)


(a)This is calculated as: total fat - (saturated fatty acids + polyunsaturated fatty acids + trans fatty acids).
(b) The percentage of total energy available after taking into account that consumed as protein and fat, hence the wide range.
(c) The term "free sugars" refers to all monosaccharides and disaccharides added to foods by the manufacturer, cook or consumer, plus sugars naturally present in honey, syrups and fruit juices.
(d) The suggested range should be seen in the light of the Joint WHO/FAO/UNUExpert Consultation on Protein and Amino Acid Requirements in Human Nutrition, held in Geneva from 9 to 16 April 2002.
(e) Salt should be iodized appropriately (6). The need to adjust salt iodization, depending on observed sodium intake and surveillance of iodine status of the population, should be recognized.
(f) See "Non-starch polysaccharides"
Non-starch polysaccharides (NSP)
Wholegrain cereals, fruits and vegetables are the preferred sources of non-starch polysaccharides (NSP). The best definition of dietary fibre remains to be established, given the potential health benefits of resistant starch. The recommended intake of fruits and vegetables (see below) and consumption of wholegrain foods is likely to provide $>20$ g per day of NSP (>25 g per day of total dietary fibre).

Antioxidants reduce women fertility

[6] A study of Shkolnik and colleagues 2011 stresses that ovulation is stimulated the pituitary luteinizing hormone (LH). This process is related to inflammation involving oxidant radicals (reactive oxygen species ROS). In their study the authors found that antioxidants reduced the rate of ovulation in rats preventing the modification of the local tissue, which prepares the ovulation.

Progesterone production was also found to be reduced by antioxidants, together with up-regulation of genes by the LH hormone which were also significantly reduced. Oxidants on their turn, were found to be implicated in phosphorylation and activation of the epidermal growth factor receptor (EGFR) and its downstream effector, p42/44 MAPK, essential elements of ovulation. More studies related to antioxidants supplements and its possible implication in reduction of fertility are needed. The authors concluded that the production of ovary oxidant radicals is essential to fertility and antioxidants may become a non-hormonal contraceptive.

Oxano and Anti-Age

Oxano and Anti-Age are produced by Merz. Both are developed to avoid or even reverse damage caused by free radicals thus acting as anti-ageing agent. Dr. Müller-Wohlfahrt has created the "Formula" for both products. In his book "How to protect your health"[7] he explains his strategy to fight free radicals in an attempt to reduce the risk of cancer and early ageing.
He suggests :
1.- Drink daily milk to supply calcium in prevention of late osteosporosis.
2.- Eat one banana for the meal between. It is rich in vitamins, minerals and new energy
3.- Eat dried fruits. They are good antioxidants and combat free radicals.
4.- For supper: Eat sliced fruits such as tomatoes and vegetables.

If these conditions cannot be maintained dietary supplements should be taken such as Oxano.
Oxano is supposed to act against jetset symptoms, fast food reactions, heavy smoking and parties. Dr. Müller-Wohlfahrt believes that people which think about dietary supplements takes care about healthy nutrition, does some sport, reduces smoking and moderates his profession.
The president of the Deutsche Gesellschaft für Sportmedizin und Prävention (German Society for Sportmedicine and Prevention) Prof Hans Hermann Dickhuth however does not agree with Dr. Müller-Wohlfahrt. According to Prof Dickhuth the antioxidants are not been proved yet by scientific researches to have any positive activity. [8]
Five times a day there should be fruits and vegetables on the menu.
Despite critics related to the activity of antioxidants the number of evidences speaking for good biochemical activities of antioxidants are growing from day to day. Linus Pauling with his book dated from 1970 was a pioneer of these ideas. [9]


Telesept and Multivitamine

Both products are example of inexpensive products which can replace the much costlier Oxano or even Anti-Age. As seen on the table the Composition of the sheep products has a wider range of ingredients. Co-enzyme Q10 and bioflavonoids can be supplied by additional products.

Nanosilimagna, nanoparticle claims controversy

[10] The report Panorama of the German TV station NDR declared in their program of 09.03.2006 that the product claim for Nanosilimagna having a higher absoption of calcium due to its nano structure was deceiving. The manufacturer of this product is Neosino Nanotechnologies which backs its claims on affirmations of a wellknown sport physician Dr. Hans-Wilhelm Müller-Wohlfahrt, doctor of the kickers of FC Bayern Munich and the German football team A strong controversy about the product arose and the German magazine Spiegel looked behind the story. Professor Markus Antonietti, Nano-researcher of the Max-Planck-Institute in Potsdam, Germany,said that consumer could get the same effect taking a low priced (less than 1 Euro) supplement instead of using the 50 Euro nano product.


NANOSILIMAGNA PROJECT Report of a Project performed for Spiegel Online [11]


The Heaney-Study

Neosino Nanotechnologies Deutschland Vertriebs-GmbH, Griesheim, Germany, markets in Germany a nutritional supplement containing calcium, silicon, and magnesium (Nanosilimagna), in which the elements concerned are said to be in the form of nano particles, and for which the manufacturer claiming a absorbability superior to that of other physical forms of the same elemental nutrients.

The news website Spiegel Online challenged the claims by the manufacturer of Nanosilimagna. Subsequently Spiegel Online asked the Osteoporosis Research Center (ORC) of Creighton University, Omaha, Nebraska, USA, to address the question of absorption of calcium and magnesium from Nanosilimagna with a specific study in 12 volunteers. As a comparator supplement, a widely used and inexpensive effervescent tablet from a German supermarket was used.

The rises in urine calcium and magnesium and the excretion of creatinine and sodium were measured during the trial. The former was to permit adjustment for possibly large variations in salt intake or salt loss on the day(s) preceding any given test.

The data generated in this study provide no evidence either for greater absorption or for faster absorption of the calcium in Nanosilimagna than from the effervescent calcium sources. By contrast, Nanosilimagna was clearly inferior to the effervescent tablet in magnesium absorption. At no time point did the magnesium excretion differ significantly from zero, a finding compatible with a conclusion of essentially zero bioavailability for the magnesium component of Nanosilimagna.

Because of the imprecision inherent in the urine excretion method, as well as the small sample size, it is not possible to exclude some small difference in absorbability of calcium from the two sources (in one direction or the other). Nevertheless there is no hint of significant superiority of Nanosilimagna in the data generated by this study.


Cherry juice and sports drinks [12]

Tart cherries are known to be rich in antioxidant and anti-inflammatory agents.

Such anti-inflammatory agents may be beneficial for the management and prevention of inflammatory diseases.

Darshan S. Kelley and colleagues propose that the flavonoids and anthocyanins in the cherries exert an anti-inflammatory effect and may lessen the damage response to exercise. [13]

In another study Declan Connolly tested the efficacy of a tart cherry cherry juice blend in preventing the symptoms of exercise-induced muscle damage. This study was published in the British Journal of Sports Medicine, demonstrating that the strength loss and pain were significantly lower in the cherry juice trial versus placebo. Relaxed elbow angle and muscle tenderness were not different between trials.

Connolly came to the conclusion that cherry juice decreased some of the symptoms of exercise-induced muscle damage. These results have important practical applications for athletes affected by strength loss and pain after damaging exercises.

Anti-Inflammatory Effects of Strawberries in Overweight/obese Individuals: Research Project, Agricultural Research Service, USDA Gov [14]

Adipose tissue is a major source of pro-inflammatory molecules, such as interleukin-6, tumor necrosis factor-, and leptin which can contribute to chronic inflammation in obese individuals.

Strawberries contain high levels of antioxidants including ellagic acid, catechins, anthocyanins, and the flavanols quercetin and kaempferol, all of which have displayed anti-inflammatory abilities.

The specific hypothesis is that strawberries contain potent anti-inflammatory antioxidants that can prevent the oxidization of LDL involved in the generation of atherosclerotic plaques, reduce the production of inflammatory cytokines in obese individuals, and suppress the immune response.

Raucher Vitamine (Vitamines for smokers)

Is an example of special products which are developed for special needs. For smokers vitamin A and provitamin A are in this case not allowed.

Diabetes and carotenoids

Although obesity and physical inactivity are known to be major risk factors for type 2 diabetes, recent evidence suggests that oxidative stress may contribute to the pathogenesis of type 2 diabetes by increasing insulin resistance or impairing insulin secretion

A Finnish study [15] by Jukka Montonen and colleagues investigated dietary vitamin E, four tocopherols, four tocotrienols, vitamin C, and six carotenoids for their ability to predict type 2 diabetes. Vitamin E intake was significantly associated with a reduced risk of type 2 diabetes.

Intakes of alfa-tocopherol, gama-tocopherol, delta-tocopherol, and beta-tocotrienol were inversely related to a risk of type 2 diabetes. Among single carotenoids, beta-cryptoxanthin intake was significantly associated with a reduced risk of type 2 diabetes. According to the authors of the study development of type 2 diabetes may be reduced by the intake of antioxidants in the diet. No association was evident between intake of vitamin C and type 2-diabetes risk.

The carotenoid beta-cryptoxanthin, found in citrus fruits had been studied. Lycopene of tomatoes and other red fruits vegetables, used as an ingredient in both functional foods and dietary supplements was not include in the study. A study from Lu Wang and colleagues from the Brigham and Women's Hospital in Boston found little evidence for an association between dietary intake of lycopene or lycopene-containing foods and the risk of type-2 diabetes and does not protect against the risk of type-2 diabetes. [16]

Serum carotenoids alfa-carotene, beta-carotene, beta-cryptoxanthin, lutein/zeaxanthin are inversely associated with type 2 diabetes and impaired glucose metabolism, beta carotene being the most active carotenoid. No significant activity was found in relation to lycopene in the study of Terry Coyne and colleagues. [17]

The development of insulin resistance in mammals with elevated expression of an antioxidant enzyme were reported in an article of McClung JP and colleagues in Proceedings of the National Academy of Sciences. They suggest that increased glutathione peroxidase 1 (GPX1) activity may interfere with insulin function by overquenching intracellular reactive oxygen species required for insulin sensitizing. This leads to the assumption too many antioxidants in the diet could actually increase the risk of diabetes. [18]

Dietary supplements rise advantages expectation that are rather detrimental [19]

Chiou et al 2011 reports that the growing consumption of dietary supplements does not improve public health. The authors stress that taking dietary supplements, such as vitamins, the consumer expects health advantages, creating an illusory sense of invulnerability that disinhibits unhealthy behaviours.

A subject group which received placebo pills, believing it contained dietary supplements, reduced exercise, preferred hedonic lifestile and were more inclined to a buffet instead of an organic meal. They walked less compared to people which knew that they received placebo pills. The authors call this phenomena a perceived invulnerability which leads to such behaviour causing dietary supplements to alternately protect or endanger health.

In another study Chiou et al 2011 found that smokers' use of dietary supplements (e.g. vitamin C, multi-vitamins) induces illusory invulnerability that in turn disinhibits smoking. Participants who believed that they were taking a dietary supplement smoked more cigarettes than did controls. Again dietary supplement created illusory invulnerability, reducing the self-regulation of smoking. The authors stress the importance to remind the public that multi-vitamins and other dietary supplements do not provide invulnerability and do not make healthy lifestyle out-dated. [20]

Extract of algae may reduce risk of cancer [21]

Kwang Hyun Cha, Song Yi Koo and Dong-Un Lee 2008 studied the antiproliferative activity of carotenoids from marine Chlorella ellipsoidea and freshwater Chlorella vulgaris. The authors found that the main carotenoid from C. ellipsoidea was composed of violaxanthin with two minor xanthophylls, antheraxanthin and zeaxanthin, and Chlorella vulgaris contained lutein.

The extract of Chlorella ellipsoidea presented a 2.5 stronger apoptosis on HCT116 cells (colon cancer cells) compared with extracts of Chlostridium vulgaris. The authors concluded that extracts of Chlostridium ellipsoidea might be useful in the prevention of human cancers. The extracts had a more powerful anti-cancer effect when used in combination than used alone. The authors stress that their results support the theory that beta-carotene and lycopene, may interfere with the development of cancer.

Cha, Koo and Lee commented former studies of Wu and colleagues [22]which reported in 2005 that Spirulina extracts inhibited human liver cancer cells, HepG2, but Chlorella extracts produced only a minor result. Cha and colleagues say that a poor result for Chlorella was probably to be related to the water extract used by Wu, whereas the actual study was performed with organic solvents giving better results.

A foregoing study by Chew and colleagues 2003, had already reported that mice fed with dietary lutein, especially at 0.002% presented inhibition of mammary tumor growth by selectively modulating apoptosis and by inhibiting angiogenesis. [23]


Vitamin B10 (PABA) necessary for proper feather formation in chicks [24]

Briggs and colleagues reported in 1943 that chicks required two water-soluble vitamins designated as vitamin B10, necessary for proper feather formation, and vitamin B11, required for growth. These vitamins were shown to be distinct from "folic acid" as measured by Streptococcus lactis R and Lacto bacillus casei.

Methods for the purification of vitamins B10 and B11 from solubilized liver were described by Briggs in 1945, differentiating them from substances with high folic acid activity. Such substances were found to have growth, feathering, and haemoglobin activity when fed alone to chicks at relatively high levels. Briggs suggests, therefore, the existence of another unknown factor necessary to maintain normal haemoglobin formation.

FDA regulation for PABA as growth promotion and feed efficiency for Feed [25]

PABA, together with microbicides is recognized by FDA as growth promotion and feed efficiency for feed for chickens and swine, using not less than 0.1 percent para-aminobenzoic acid or the sodium or potassium salt or para-aminobenzoic acid by weight of feed.

The usual dose of PABA for humans is between 30 to 100 mg. three times a day, 50 mg being mostly indicated. Natural source of PABA: Bran, eggs, kidney, liver, molasses, wheat germ, brewer's yeast, whole grains, yogurt, mushrooms, and spinach. In humans,PABA is biosynthesized by intestinal bacteria.

PABA promoting thyroid carcinogenesis in rats initiated with N-bis(2-hydroxypropyl) nitrosamine [26]

Hasamura and colleagues (2005) found that PABA exerts promotion/progression effects on rat thyroid carcinogenesis as a result of hypothyroidism followed by negative-feedback via the thyroid-pituitary axis.

Carcinogenesis of PABA in sunscreen formulation [27]

In the past, PABA has been widely used as UV filter in sunscreen formulations. However, it has been determined that it increases the formation of a particular DNA defect in human cells, thus increasing the risk of skin cancer in people who lack the mechanisms to repair these cellular defects [28]. Currently, safer and more effective derivatives of PABA, such as octyl dimethyl PABA.

Gasparro and colleagues (1998) in a review of sunscreen safety and efficacy concluded that sunscreen ingredients or products do not pose a human health concern. [29]

Cinnamon extract and diabetes mellitus 2 [30]

Cinnamon (Cinnamomum cassiae) bark used as spice is now being studied by B. Mang and colleagues for its effect of on glycated haemoglobin A1c HbA1c, fasting plasma glucose, total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triacylglycerol concentrations in patients with diabetes mellitus type 2.

Previous studies had found that cinnamon have a positive effect on the glycaemic control and the lipid profile in these patients.

The scientists conclude that aqueous cinnamon extract has a moderate effect in reducing fasting plasma glucose concentrations in diabetic patients with poor glycaemic control.

The aqueous extract is with methylhydroxychalcone polymer as active substances, is nearly free of allergic oil present in powder of cinnamon is therefore safe for allergic patients.

Cinnamon extract reducing oxidative stress [31]

Dr. Anne-Marie Roussand colleagues presented the results of a researcher on a group of 24 patients with impaired fasting glucose levels at the 47th annual meeting of the American College of Nutrition in 2006.

In this study Malondialdehyde (MDA) was chosen as an indicator of oxidative stress.
Plasma antioxidant levels were measured by ferric-reducing ability of plasma (FRAP) and plasma SH (thiols). were both significantly increased, After 12 weeks of 500 gram cinnamon extract supplementation there was a reduction of malondialdehyde.

The authors found a reduction in blood glucose levels, triglycerides, LDL cholesterol and total cholesterol. All the participants had type-2 diabetes. Cinnamon extract in this study, caused an increase of plasma antioxidant levels. According to Dr. Richard Anderson the active compounds found in cinnamon extract may be helpful in reducing the risk of these diseases by providing cells protection from harmful oxidation and may reduce risk of metabolic syndrome which causes central obesity, hypertension, and unstable glucose and insulin metabolism.

Whole cinnamon and aqueous Extracts Ameliorate Sucrose-Induced Blood Pressure Elevations in Spontaneously Hypertensive Rats [32]

Dr Anderson and colleagues report that cinnamon and a cinnamon extract could reduce blood pressure in spontaneously hypertensive rats, according to a study of 2006.

Diabetes Care: Cinnamon Improves Glucose and Lipids of People With Type 2 Diabetes [33]

Alam Khan and colleagues found that 1g of cinnamon per day reduced blood glucose levels, as well as triglycerides, LLD cholesterol, and total cholesterol in a small group of people with type-2 diabetes. The authors suggest that the inclusion of cinnamon in the diet of people with type 2 diabetes will reduce risk factors associated with diabetes and cardiovascular diseases.

Cinnamon Supplementation Does Not Improve Glycemic Control in Postmenopausal Type 2 Diabetes Patients [34]

Vanschoonbeek and colleagues concluded that cinnamon supplementation (1.5 g/d) does not improve whole-body insulin sensitivity or oral glucose tolerance and does not modulate blood lipid profile in postmenopausal patients with type 2 diabetes. The authors call for more research on the proposed health benefits of cinnamon supplementation, until then no health claims should be made.

Antioxidant potential of cinnamon tea [35]

Akram Ranjbar and colleagues 2006 studied the antioxidative stress capacity of cinnamon tea (Cinnamomum zeylanicum) in humans for 2 weeks. The authors found an increased in total antioxidant power and total thiols but a decrease in lipid peroxidation levels, compared with regular tea. The authors concluded that the antioxidant potential of cinamon tea may reduce the complications related to oxidative stress.

Antidiabetic effect of Cinnamomum cassia extract [36]

According to Verpohl, Bauer and Neddermann 2005 Cinnamomum cassia bark or extracts from Cinnamomum cassia and zeylanicum exerted an effect on blood glucose and plasma insulin levels in rats. The cassia extract was found to be superior to the zeylanicum extract. The extract of cassia was slightly more efficacious than its bark.

The authors concluded that acassia extract reduced the blood glucose levels in a glucose tolerance test (GTT), and plasma insulin production was elevated responding to an in vitro stimulatory effect of insulin release from INS-1 cells. Cassia extract is, therefore, considered to have a direct antidiabetic effect.

Toxicity concerns of cinnamon [37]

Coumarin is a flavouring which is found in higher concentrations in the types of cinnamon grouped together under the name "cassia cinnamon". Relatively small amounts of coumarin can already damage the liver of particularly sensitive individuals. However, this is not permanent damage. Isolated coumarin may not be added to foods.

Synthetic coumarin is used in cosmetics. It smells of fresh hay. Coumarin is also used for medicinal purposes to treat oedemas. Isolated coumarin may not be added to foods.

A rough distinction can be made between two types of cinnamon. Ceylon cinnamon only contains low levels of coumarin which are safe from the risk assessment perspective. By contrast, cassia cinnamon contains high levels of coumarin and large amounts of this cinnamon should not, therefore, be eaten.

It is almost impossible for consumers to distinguish between Ceylon cinnamon and Cassia cinnamon. If coumarin-containing plant parts like cinnamon are used for flavouring, then the amount of coumarin is limited to 2 milligrams per kilogram food according to the Flavourings Ordinance.

Food manufacturers and importers are responsible for ensuring compliance with maximum levels. BfR has assessed the potential health risk from coumarin in foods. It believes there is a risk of liver damage in particularly sensitive individuals. BfR has, therefore, established a tolerable daily intake (TDI). This amount can be consumed over a lifetime without posing a risk to health. The TDI is 0.1 milligram coumarin per kilogram body weight and day. This also applies to particularly sensitive individuals. The European Food Safety Authority (EFSA) decided on the same value in its coumarin assessment.

Safflower extract reduces risk of renal fibrosis [38]

Akram Ranjbar and colleagues 2006 studied the blood-circulation-promoting Chinese herb, safflower, on fibrosis status in NRK-49F cells, and the mechanism of transforming growth factor-beta (TGF-beta), a potent fibrogenic growth factor. They found that safflower extract can suppress renal cellular fibrosis by inhibiting the TGF-beta autocrine loop, and less tissue collagen were noted in the nephron and serum TGF-beta1 compared with the untreated controls.

The authors concluded that safflower extract inhibits renal fibrosis by down-regulating TGF-beta signals.


Cassia gum as gelling agent and thickener in foods [39]

The European Food Safety Authority (EFSA) says that cassia gum as gelling agent and thickener in foods is not of safety concern.

Cassia gum is the flour from the purified endosperm of seeds from Cassia tora and Cassia obtusifolia.

Cassia gum is intended to be used ice cream and frozen milk desserts certain baked goods soup mixes, sauces and selected oil-free salad dressings, yoghurt, sausages, corned beef, and canned poultry meats at levels up to 1.5 g/kg and in all other applications at levels up to 2.5 g/kg.

Galactomannans are recognised as components of dietary fibre and are resistant to digestive enzymes in the gastrointestinal tract.

According to EFSA it is expected that cassia gum is excreted unchanged. Fermentation of cassia gum by gut microflora may occur to a small extent. However, the Panel notes that any hydrolysed material would represent oligo- or monosaccharides that can be expected to be absorbed and metabolised in normal biochemical pathways.

Long-term carcinogenicity studies on cassia gum were not available. Other related galactomannan gums, including locust (carob) bean, guar gum and tara gum were not carcinogenic when fed to mice and rats. Given that cassia gum is not genotoxic, and that many other related galactomannan gums are not carcinogenic, the Panel does not consider long-term carcinogenicity studies essential for the safety assessment of cassia gum.

According to the EFSA panel the presence of seeds of Cassia occidentalis for the preparation of cassia gum should be less than 0.1 % selected by colour and shape.

Conclusion

Given these results from the toxicological studies, the very low absorption of cassia gum and the fact that, if hydrolysed at all, cassia gum would be degraded to compounds that will enter normal metabolic pathways, the EFSA Panel concludes that the use of cassia gum complying with the newly defined specifications as an additive for the proposed food uses is not of safety concern.

Cassia occidentalis:

Cassia occidentalis (Syn.: Senna occidentalis) has been found by Tasaka to be toxic to heart and liver leading to death in rabbits and muscle necrosis in pigs by Tim. [40] [41]

Cassia occidentalis is suggested to have antibiotic activity, immunostimulant actions, liver protective and detoxification actions, antimutagenic actions, laxative actions, anti-inflamatory and anti-spasmotic actions, antimalarial and antiparasitic actions. [42]


Beta glucan

Beta Glucan is primarily cultured extract of Baker's Yeast cell wall. It is used as an immunostimulant. Beta glucans are sugar molecules (polysaccharides).

Polysaccharides or polysaccharide-protein complexes are considered as multi-cytokine inducers that are able to induce gene expression of various immunomodulatory cytokines and cytokine receptors.

Some interesting studies focus on investigation of the relationship between their structure and antitumor activity, elucidation of their antitumor mechanism at the molecular level, and improvement of their various biological activities by chemical modifications. [43]

In Japan, extracts containing various types of Beta glucan have been used to successfully assist in treating cancer patients for the last 20 years. See Aoki, T. Chapter 4, Lentinan. In: Modulation Agents and their Mechanism. Richard L. Fenichel (Ed), Marcel Dekker, Inc., New York and Basel, pp 63-77 (1984). [44]

The two primary uses of beta-glucan are to enhance the immune system and to lower blood cholesterol levels. Numerous experimental studies in test tubes and animals have shown beta-glucan to activate white blood cells. [45], [46]

Beta-glucans [47]

Beta-glucans) are polysaccharides that only contain glucose as structural components. They occur in the bran of cereal grains, the cell wall of baker's yeast, certain types of fungi, and many kinds of mushrooms. The cereal based beta-glucans occur most abundantly in barley and oats and to a much lesser degree in rye and wheat. They are useful in human nutrition as texturing agents and as soluble fiber supplements.
One of the most common sources of Beta 1,3-D glucan is derived from the cell wall of baker's yeast (Saccharomyces cerevisiae), which are often insoluble. Those extracted from grains tend to be both soluble and insoluble.

Rice starch and beta-glucan [48]

Rawiwan Banchathanakij and Manop Suphantharika analysed the rice starch, its interactio9n with beta-glucan preparation, and conducted textural analysis. All tested beta-glucans reduced the retrogradation of the rice starch gels under cold storage. The soluble oat and barley beta-glucans were more effective in reducing retrogadation than the insoluble curdlan and yeast beta-glucans. All beta-glucans did not affect gelatination behaviour of the rice starch.// // The authors stress that the effects are not related solely to beta-glucan, but also to their molecular weight and structure, and impurities. The authors point out that, aside of its rheologic properties, the beta-glucans are being studied because of their immune stimulation, anti-inflammatory, antimicrobial, antitumoural, heptoprotective and cholesterol-lowering properties. [47]

Concentrated oat beta-glucan, a soluble fibre as new supplement for cholesterol reduction. [49]

Joanne Slavin and colleagues studied soluble fibre such as a concentrated oat beta-glucan on its effects on cardiovascular disease endpoints in human subjects.

Fermentability

In this study the fermentability of concentrated oat beta-glucan with inulin and guar gum in a model intestinal fermentation system was compared. It has been reported that fermentation products like propionate and acetate may suppress cholesterol synthesis and contribute to cholesterol lowering. All three were found to produced similar concentrations of short chain fatty acids and acetate, however, the oat beta-glucan was found to produce the highest concentrations of butyrate at 4, 8, and 12 hours, after which inulin produced the most.

The authors found in their study that six grams concentrated oat beta-glucan per day for six weeks significantly reduced total and LDL cholesterol in subjects with elevated cholesterol. No significant changes were observed in HDL cholesterol, glucose, insulin, homocysteine or C-reactive protein (CRP) as a result of the beta-glucan intervention. This oat beta-glucan was fermentable, producing higher amounts of butyrate than other fibers.

The authors concluded that a practical dose of oat beta-glucan can significantly lower serum lipids in a high-risk population and may improve colon health. The authors also stress the fact that concentrated oat beta-glucan is suitable as a "stand-alone" supplement for cholesterol reduction, it can also be used as a food ingredient to increase fibre content of food.

Anti-atherosclerotic activity of avenanthramides from oat [50]

According to Chen and colleagues 2007 avenanthramides, alkaloids which occurre only in oats, may have anti-atherosclerotic activity. The authors found that after consumption of 1 g avenanthramide-enriched mixture extracted from oats, plasma reduced glutathione was elevated by 21% at 15 min and by 14% at 10 h .

The authors concluded that oat avenanthramides are bioavailable and increase antioxidant capacity in healthy older adults.


Greenish colour of oats and oat products is related to leavening agents and ferrous iron [51]

Doehlert, Simsek and Wise 2009 studied greenish colouring of steel cut oath when cooked. They found that ferrous iron (as little as 10 ppm Fe++) of tap water may cause a green gray colour on the seed coat of oats. This is more accentuated on steel cut groats where the seed coat layer is less disrupted than in oat flakes.

The authors recommend to let cooking water stand for a few hours so ferrous iron (Fe++) can react with atmospheric oxygen to form ferric iron (Fe+++) forming a cloudy precipitate which settles out. Using the supernatant water the colour of the oats will not be affected. Alkaline conditions (pH 9-12) may cause brown-green colour during cooking. Leavening agent such as bicarbonate (50 mM NaHCO3) may create such conditions during backing. This is associated with the phenolic acid or avenanthramide content of the oat. The authors also found that aleurone stained darker than the starchy endosperm. Calcium (Ca++) and magnesium (Mg++) had no colouring effect.

Garlic and garlic supplements without effect on hipercholesterolemia [52] [53]

Garlic (Allium sativum) and wild garlic (Allium ursinum)are used since long for treatment of cardiovascular and infectious diseases as antioxidant and also because of anticancer properties. Garlic supplements are therefore promoted as cholesterol-lowering agents. Crushing garlic promotes the formation of allicin which is told to be responsible for the activity of garlic.

Gardner et al. evaluated the effect of raw garlic and two commonly used garlic supplements on cholesterol concentrations in adults with moderate hypercholesterolemia.

The researchers found no statistically significant effects of garlic on blood lipids.

They conclude that none of the forms of garlic used in this study, including raw garlic, when given at an approximate dose of a 4-g clove per day, 6 d/wk for 6 months, had statistically or clinically significant effects on LDL (low-density lipoprotein cholesterol), HDL (high-density lipoprotein cholesterol), triglyceride levels, or total cholesterol-high-density lipoprotein cholesterol ratio in adults with moderate hypercholesterolemia.

According to this study physicians can advice patients with moderately elevated LDL cholesterol concentrations that garlic supplements or dietary garlic in reasonable doses are unlikely to produce lipid benefits.

The authors, however, stress the fact that this trial should not be generalized to other populations or health effects. Garlic might lower LDL in specific subpopulations, such as those with higher LDL concentrations, or may have other beneficial health effects.

Weight reduction ingrediets

Ephedra sinica (Ma huang) contains ephedrin. The FDA banned the use of Ephedra and dietary supplements containing ephedrin (an alcaloid) as an unreasonable risk of illness or injury in April 2004.

Some species in the Ephedra genus have no alkaloid content and are therefore essentially inert; however, the most commonly used species, Ephedra sinica, has a total alkaloid content of 1-3% by dry weight. Ephedrine constitutes 40-90% of the alkaloid content, with the remainder consisting of pseudoephedrine and the demethylated forms of each compound.

In February 2007 FDA reaffirmed the ban of Ephedra products saying that no dosage of dietary supplements containing ephedrine alkaloids is safe and the sale of these products in the United States is illegal and subject to FDA enforcement action. [54]

Ingredients for weight loss with unproved effectiveness are guarana, yerba mate, ginseg, guar gum, psylium,lichorice, algae, apple cider vinegar and others. The only way to get rid of some extra pounds is to reduce intake of calories and to increase energy expediture such as sport.

Illegal ephedra plant based drug used as "fat burner"linked with death in Denmark [55]

The Danish Medicines Agency (DMA) reports a recent death caused by the Therma Red, which is being used to loose weight and to boost performance of sportspeople. The product contains ephedrine and caffeine in extremely high concentrations. Serious reactions are expected, such as increased blood pressure and blood clotting. The DMA issued a warning of products containing ephedra and ephedrin.

Ephedrine is a stimulant and thermogenic, also known as ma huang. It is not allowed as a food or supplement ingredient in the European Union, US and other states. It caused several death.

The plant Ephedra sinica contains the alcaloids ephedrin and pseudoephedrin as active constituents. Haller and Benowitz 2000 report adverse events related to the use of supplements containing ephedra alkaloids such as hypertension, palpitations, tachycardia, stroke, and seizures. These effects resulted in death, and permanent disability. [56]

Instead of using dangerous supplements exercise and low fat and low caloric diet are recommended. Instead of beer drink green tea with no sugar, or just choose sparkling mineral water as a drink at the bar.

Pros and cons related to supplements

The vitamin E study [57]

A 10 per cent increased risk of mortality for people taking 400 International Units per day of vitamin E were reported by Miller and colleagues in 2005.

A meta-analysis of 19 randomized, controlled trials involving more than 135 000 participants found that high-dosage vitamin E supplementation (400 IU/d for at least 1 year) increased all-cause mortality. The effects of lower-dosage supplementation were unclear. The authors concluded that high vitamin E supplementation should be avoided.
This study has been highly criticised and discredited as flawed.

The Bjelakovie meta-analysis 2007 [58]

Goran Bjelakovic and colleagues report results of a systematic literature review to assess the effects of beta carotene, vitamins A and E, ascorbic acid (vitamin C), and selenium on all-cause mortality among participants in primary and secondary disease prevention trials.

Bjelakovic and colleages excluded studies which did not match the criteria of his meta-analysis. Only 68 randomised trials were included in the meta-analysis, comprising beta-carotene doses ranging from 1.2 to 50 milligrams, vitamin A from 1333 to 200 000 International Units (RDI 5000 IU, Upper Safe Limit 10,000 IU), vitamin C from 60 to 2000 mg (RDI 60 mg, UL 2000 mg), vitamin E from 10 to 5000 IU (RDI 30 IU, UL 900 IU), and selenium from 20 to 200 micrograms (RDI 65 micrograms, UL 450 micrograms).

The authors found that beta carotene, vitamin A, and vitamin E, taken singly or combined with other antioxidant supplements, were associated with increased all-cause mortality. The authors conclude that treatment with beta carotene, vitamin A, and vitamin E may increase mortality. The potential roles of vitamin C and selenium on mortality need further study.

The authors say that although oxidative stress has a hypothesized role in the pathogenesis of many chronic diseases, it may be the consequence of pathological conditions. By eliminating free radicals from our organism, we interfere with some essential defensive mechanisms.

Critics on the Bjelakovie meta-analysis

Meir Stampfer, a professor of nutrition and epidemiology at the Harvard School of Public Health points out that the studies reviewed were too different to be able to pool them together.

Andrew Shao, vice president of the US-based Council for Responsible Nutrition said that the combined studies were far too diverse and different in terms of dosage, duration, study population and nutrients tested that the results of the analysis were compromised. According to Dr. Shao most of the trials included in the meta-analysis tested for secondary prevention in diseased populations, instead of primary prevention studies in healthy populations. Combining secondary prevention and primary prevention trials and then making conclusions for the entire population is an unsound scientific approach.

Vitamin E supplements may increase risk of lung cancer [59]

Christopher Slatore and colleagues 2007 assessed the association of the incidence of lung cancer and supplemental multivitamins such as vitamin C, vitamin E, and folate.

The authors found that daily use of supplemental multivitamins, vitamin C, vitamin E, and folate did not reduce the risk of lung cancer. Supplemental vitamin E was even associated with a small increased risk of lung cancer in current smokers, the greatest incidence was found for non-small cell lung cancer.

Study finds no reduction of cancer risk with vitamin C, E and beta carotin supplementation [60]

Jennifer Lin and colleagues 2009 assessed the prevention of cancer due to a diet high in fruits and vegetables, rich in antioxidants.

Supplementation of vitamin C (500 mg of ascorbic acid daily), natural-source vitamin E (600 IU of alfa-tocopherol every other day), and beta carotene (50 mg every other day) during an average 9.4 years of treatment no statistically significant effects of use of any antioxidant on total cancer incidence was found. Duration and combined use of the three antioxidants also had no effect on cancer incidence and cancer death.

The authors concluded that supplementation with vitamin C, vitamin E, or beta carotene offers no overall benefits in cancer prevention.

Commentary on the study of Lin and colleagfues 2009 [61]

Demetrius Albanes, of the National Cancer Institute, stresses that negative trial data reported by Lin, the trend for a reduction in colon cancer with vitamin E supplementation, found in other studies, should not be forgotten. Beta carotene found by Linn to be associated with a modest excess of lung cancer, is consistent with previous reports. Overall Albanes says that even negative findings such as those of the Linn study add to a better understanding of the causes of cancer.

Slimming ingredients, an unserious category?

Chitosan can be used in water processing engineering as a part of a filtration process. Chitosan causes the fine sediment particles to bind together and is subsequently removed with the sediment during sand filtration. Chitosan also removes phosphorus, heavy minerals, and oils from the water. [62]

Chitosan is also useful in other filtration situations, is used to clarify wine, mead and beer, improves flocculation, and removes yeast cells, fruit particles, and other detritus that cause hazy wine.

Chitosan is supposed to have the capability of attracting fat from the digestive system and expelling it from the body so that users can, it is claimed, lose weight without eating less. However, some scientific research suggests that these claims are likely without substance. [62]

With the unavailability of specific research studies to support the claims made on chitosan as a revolutionary weight loss supplements, one must be careful on what is fact and what is speculation. [62]

Chitosan reduces cholesterol and body weigt gain [63]

Dr. Shahdat Hossain and colleagues from Jahangirnagar University, studyed the effects of chitosan extracted from locally sourced shrimps Macrobracium rosenbergii using sequential decalcification, deproteination, deacetylation and the acid-extraction of chitin.on bodyweight, plasma lipid profile, fatty acid composition, liver lipid peroxide levels and plasma levels of glutamate pyruvate transaminase.

The authors found that dietary supplementation of chitosan decreases the atherogenic lipid profiles of both NC and HC rats and reduces the bodyweight gain of HC rats.

Adequate anti-oxidants should be added to chitosan-enriched supplements in order to minimize the degree of oxidative stress to the liver. Further studies should clear whether the benefits of chitosan noted in rats are also translated into humans.

International Conference on Innovations and Trends in Weight Loss and Weight Management [64]

At the First International Conference on Innovations and Trends in Weight Loss and Weight Management held in March 2007 in Berlin Dr. Jorg Gruenwald reviewed the European market of slimming ingredients and stated that the science supporting chitosan's benefits was limited. He Is a leading European expert in the field of botanicals and natural products.

According to an overview by Dr. Gruenwald, the slimming ingredients market can be divided into five groups based on the mechanisms of action: According to Dr. Gruenwald supplements with weight reduction claims with various levels of supporting scientific evidence are green tea polyphenols, CLA, Hoodia gordonii, DHEA, hydroxy-methylbutyrate (a metabolit of leucine), and chromium picolinate, leading down to ingredients with only limited available data, like L-carnitinewith only limited available data, like L-carnitine, calcium and chitosan.

The conference called for industry to make more effort with academia and clinical trials to obtain credibility.

Chitosan supplementation and fecal fat excretion [65]

Chitosan-based supplements are sold as fat trappers and fat magnets. Matthew Gades and Judith Stern quantified the in vivo effect of a chitosan product on fat absorption. In this study the authors concluded that the fat trapping claims associated with chitosan are unsubstantiated with no significant effect on energy balance.

Chitosan supplementation and fat absorption [66]

Chitosan is a primary ingredient in dietary weight-loss supplements. Its claimed activity is the binding and trapping of dietary fat, leading to fat excretion and weight loss without caloric restriction. Gades and Stern (2005) tested the fat-trapping capacity of a chitosan product in men and women.

The author conclude that the fat trapped was clinically insignificant. The product fails to meet claims.

Weight loss supplements [67]

According to Judith S. Stern there are not any supplements that cause substantial weight loss. Consumer rely on testimonials, and they erroneously assume that supplements are safe because they believe the federal government would not allow unsafe products on the market.

Unfortunately, the federal government has limited power and money to stop the marketing of such supplements. According to the Dietary Supplement Act (DSHEA) of 1994, supplement manufacturers are not required to perform premarketing safety evaluations of their products. DSHEA leaves it to the federal government to prove that a specific supplement is not safe. The FDA and FTC simply do not have the budget to do that job.

In April 2004, the Food and Drug Administration (FDA) made an effort in ensuring public safety by sending warning letters to 16 dietary supplement distributors for making false and misleading claims for weight-loss products promoted over the Internet. [68]

Minimal effect of chitosan on body weight [69]

Ni Mhurchu and colleagues, in a review of studies related to chitosan, come to the conclusion that there is some evidence that chitosan is more effective than placebo in the short-term treatment of overweight and obesity. However, many trials to date have been of poor quality and results have been variable. Results obtained from high quality trials indicate that the effect of chitosan on body weight is minimal and unlikely to be of clinical significance.

Adequate anti-oxidants should be added to chitosan-enriched supplements in order to minimize the degree of oxidative stress to the liver. Further studies are certainly needed to clarify these aspects of chitosanand wether the benefits of chitosan noted in rats are also translated into humans.

Touchi Extract [70]

Touchi is a fermented soy bean extract that has been used for centuries in Asia. It is a protein-rich product in powder form obtained by aqueous extraction of small soybeans that have been fermented using the fungus Aspergillus Oryzae , also known as "salted black beans".

An application to the UK Food Standards Agency (FSA) requests to use touchi in food supplements and make health claims to combat metabolic syndrome, a collection of conditions associated with obesity and type-2 diabetes. It was lodged by a Japanese distributor, CBC Co Ltd planing to market the ingredient as a food supplement and a tea/soup style formulation at levels that would not exceed 4.5 g per daily serving/dose. One portion of black bean sauce contains 15g of fermented black beans, which corresponds to 4.5 g of Touchi extract.

Alpha-glucosidase Inhibitory Action [71]

According to CBC Co Ltd touchi extract can inhibit alpha-glucosidase action, when consumed as a food supplement alongside a meal. It can delay carbohydrate digestion in the small intestinal tract.

Undigested carbohydrates or disaccharides are then excreted rather than being absorbed by the body thus providing possible assistance in weight control regimes. CBC points out that the inhibition of alpha-glucosidase is found only in beans fermented with Aspergillus sp.; it is absent in the raw or boiled bean, in bean whey or in beans fermented with Bacillus subtilis natto (a traditional Japanese appetiser). According to the UK FSA touchi will be marketed at anyone who wants to slow the breakdown of carbohydrates.

Antihyperglycemic effect of touchi extract [72]

Hiroyuki Fujita and colleagues 2001 found that water-extracted touchi presented antiglycemic effect at a minimum effective dose of 0.3 g. The researchers gave 0.3 g Touchi extract to diabetics before eating 200 g of cooked rice, the postprandial increases in blood glucose and mean insulin levels were significantly depressed, compared with levels when no TE was administered. This effect was due to the alpha-glucosidase inhibitory activity of the extract. The authors suggest touchi extract in the management of patients with non-insulin-dependent diabetic mellitus.

Powdered Houji-tea long-term ingestion [73]

The effects of powdered Houji-tea was studied by Fujita and coleagues 2001 in humans with borderline and mild type-2 diabetes. All subjects ingested Houji-tea with or without 0.3 g of TE before each of three meals per day for 3 mo. The alpha-glucosidase inhibitory TE demonstrated an antihyperglycemic effect and may prove useful for improving glycemic control in subjects suffering from borderline and type-2 diabetes mellitus.


Conjugated Linoleic Acid (CLA) as food supplement

Some substances can create a supplementation of food such as the Conjugated Linoleic Acid (CLA)[74]. It is a group of natural geometrical and position isomers of linoleic acid. A generical definition says that conjugated fatty acids are polyunsaturated fatty acids in which at least one pair of double bonds are separated by only one single bon such as:-C=C-C=C-. The most important of these fatty acids is produced by bacterial fermentation in the digestive system of ruminants, being found in milk and meat of these animals.
It is called rumenic acid(cis 9, trans 11, octadien acid)
The bacterium which isomerates the linoleic acid to CLA is Butyrivibrio fibrisolvens.

The conjugated linoleic acids are told to improve the resistance to carcinogenic diseases and to reduce the body fat. The natural amount of CLA in milk and meat is to small to induce anticarcinogenic and anti fat activities. CLA enriched oil is commercially available and can be used to supplement foods such as margarine, chococream, backery products and dairy products.


Claims of CLA acids are

1. Anticarcinogenic

This action was observed on mice.

2. Antiaterogenic

This action is not well known. Further studies are necessary.

3. Anabolic effect

Rumenic acid seems to reduce the body fat increasing at the same time the fat-free body mass (lean body mass). Muscle tissue and bone mass increases.It is why Conjugated Linoleic Acids are found in the formula of some anabolic preparations.

4. Activity on the immunological system

The immunoglobulinesIgA, IgG and IgM are increased and EgE reduced. This reduces the the risk of allergy

5. Antidiabetic

An antidiabetic activity of the CLA acids was found in rats.

6. Antithrombotic

The CLA acid group has a strong antithrombotic activity, contrary to linoleic acid which increases thrombotic.
CLA is present in milk, milk derivates, meat and its derivates of ruminants. [75]
Food CLA (rumenic acid)
  in total fatty acids
   
Milk and derivates 0,86%
Meat and derivates 0,6%
Cakes and cookies 0,32%
Fish 0,05%
Chocolate 0,14%
Margarine, edible  
oil,fats and chips <0,01%



The amount of CLA in milk and derivates can easily increased up to 500 times giving animal feed enriched with linolein acid such as sunflower oil, about 50 g/kg dry feed[76]. Chemical synthesis is very difficult.
Biological activity of lactobazillus, Candida antarctica have been tried to produce CLA, with minor success. Promising is the way of animal feed enriched with linoleic acid. Milk, its derivates and meat of ruminants being fed with such animal feed is a natural biological way to increase CLA as functional food.

Antidiabetic effects of CLA mediated via anti-inflamatory effects in adipose tissue [77]

Helen M. Roche and colleagues investigated whether dietary fatty acids could attenuate the proinflammatory insulin-resistant state in obese adipose tissue which may be the source of insulin desensitizing proinflammatory molecules that predispose to insulin resistance.

The authors found that c9,t11-Conjugated Linoleic Acid inhibited tumor necrosis factor-alfa-induced downregulation of insulin receptor substrate 1 and GLUT4 mRNA expression and promoted insulin-stimulated glucose transport in 3T3-L1 adipocytes compared with linoleic acid. The authors suggest that altering fatty acid composition may attenuate the proinflammatory state in adipose tissue that predisposes to obesity-induced insulin resistance.

Conjugated Linoleic Acid (CLA), a review

[78] Conjugated linoleic acid was proposed as supplement improving body composition, cancer prevention, diabetes, high cholesterol. It also has been promoted as a fat burning supplement. According to Emory Healthcare, however, there is little evidence that it works, and growing evidence that CLA might actually worsen blood sugar control in people who are overweight.

The typical dosage of CLA ranges from 3 to 5 g daily even very small amounts of a toxic contaminant can quickly add up if low quality of CLA is used, warns Emory Healthcare.


Conjugated linoleic acid production in gut [79]

Devillard and colleagues (2007) found that the human gram-positive intestinal Roseburia spp.species were among the most active bacteria metabolizing linoleic acid (cis-9,cis-12-18:2) and vaccenic acid (trans-11-18:1) or a 10-hydroxy-18:1, which are precursors of conjugated linoleic acid.

Voevodin and colleaugues (2005) in a meta-analysis found only minimal benefits, whether for weight or body composition, the evidence being more negative than positive in relation to weight loss supplement. [80]

CLA does NOT appear to be a useful supplement for people with diabetes, and might in fact contribute to diabetes in overweight people. CLA might decrease insulin sensitivity, creating a pre-diabetic state. [81] [82] [83]. However, Syvertsen and colleagues did not find any harmful effect. [84]
Emory Healthcare advices at present individuals with diabetes or at risk for it not to use CLA except under physician supervision. [78]

One study found that CLA impairs endothelial function, suggesting that it might increase cardiovascular risk. [85]

A small double-blind trial found weak evidence that CLA might be useful for high cholesterol. [86]

Some animal and test tubes suggesting that CLA might help prevent cancer are based on animal and test tube researches, evidence is preliminary and inconsistent. [87] [88]
One study failed to find that CLA can enhance immune function. [89]

CLA and nursing mothers

Concerns have also been raised regarding use of CLA by nursing mothers. A study found that CLA reduces the fat content of human breast milk. [90]

Since infants depend on the fat in breast milk to provide adequate calories and on certain fats to aid proper growth and development, it is probably prudent for nursing mothers to avoid CLA supplements. [78]
Maximum safe dosages of CLA for young children, pregnant women, or those with severe liver or kidney disease have not been determined. [78]

Memory Supplements without solid scientific support

According to a review [91]of the Center for Science in the Public Interest (CSPI), there is no solid science indicating that any of the major ingredients of dietary supplements help protect or improve memory.

Antioxidants

Antioxidants are common ingredients in memory supplements, particularly lipoic acid and the Asian plant bacopa. The single study of lipoic acid's effect on cognition found that it didn't help HIV patients with dementia. Of three Australian studies of bacopa, one found that 23 adolescents scored higher on memory tests but two bigger studies of middle-aged and older people found no effect.

Vitamin E

Kang and colleages found in a study published in 2006, that long-term use of vitamin E supplements did not provide cognitive benefits among generally healthy older women. [92]

No reduction of vascular diseases with antioxidants

The Heart Protection Study Collaborative Group 2002, made a study with 20 536 UK adults with coronary disease, other occlusive arterial disease, or diabetes. The Group wanted study the suggestion that increased intake of various antioxidant vitamins reduces the incidence rates of vascular disease, cancer, and other adverse outcomes. The patients received antioxidant vitamin supplementation (600 mg vitamin E, 250 mg vitamin C, and 20 mg beta-carotene daily) This suplementation did not produce any oxidative stress study, model for future studies [93]
Jackson Roberts and colleaugues determined the dosage of vitamin E that decreases systemic oxidant stress in humans.
The dose-dependent effects of vitamin E-alfa tocopherol was measured by the concentration of F2-isoprostanes, a biomarker of free radical-mediated lipid peroxidation.

Foregoing clinical trials had found no significant effects of vitamin E regarding protection against heart attack. The present study suspects that the studies had been poorly designed. The researchers say that these trials used a single dose of vitamin E and only looked for end points such as heart attack occurrence.

In the present study the authors found a linear trend between the dosage of vitamin E and percentage reduction in plasma F2-isoprostane concentrations which reached significance at doses of 1600 IU (reduction of 35 per cent) and 3200 IU (reduction of 49 per cent).

In vitro studies that vitamin E may act as a pro-oxidant at certain concentrations were not backed by this study.

The study informs the planning and evaluation of clinical studies that assess the efficacy of vitamin E to mitigate disease, and can serve as a model for further studies.

L-arginine supplementation improves arterial responses in disease with endothelial dysfunction [94]

According to Guttman and colleagues 2010 longterm supplementation of L-arginine improves large artery elasticity index (LAEI) in patients with multiple cardiovascular risk factors, and decreased systolic blood pressure, peripheral vascular resistance as well as a decrease in aldosterone levels. The authors stress that long term L-arginine supplementation may improve artery compromised by disease with endothelial dysfunction.

Long-term treatment with antioxidants (vitamin C, vitamin E, coenzyme Q10 and selenium) improves artery health, humoral factors and inflamatory markers in case of multiple cardiovascular risk [95]

Shargorodsky and colleagues 2010 report that daily oral supplementation with vitamin C (1000 mg/day), vitamin E (400 i.u/day), coenzyme Q10 (120 mg/day) and selenium (200 mcg/day) during six month improved the large arterial elasticity index (LAEI) as well as small arterial elasticity index (SAEI). HbA1C was reduced and HDL-cholesterol was increased.

The authors concluded that antioxidant supplementation significantly improved vascular health, glucose and lipid metabolism as well as decrease in blood pressure.

Neurotransmitters [96]

Neurotransmitters relay signals from one nerve cell to another. A building block of one such neurotransmitter involved in memory is choline. However, studies show that in supplement form choline doesn't even reach the brain. No study has found DMAE, a building block of choline, to be helpful for memory, and several tests have found it not to be useful for Huntington's or Alzheimer's patients. B vitamins are included in some products because they can lower levels of homocysteine in blood, and high levels of homocysteine are linked to poor cognition. One Dutch study found that folic acid helped more than a placebo in folate-deficient volunteers, but grain-based foods in the U.S. are already fortified with folic acid (the Dutch study looked at folate-deficient volunteers.) Seventeen of the 18 other studies showed no effect of B vitamins on memory.

Ginkgo biloba

Ginkgo biloba helps increase blood flow, and is included in many memory formulas, yet studies are inconclusive at best. The most recent tests showed ginkgo takers scored better on just one of 14 tests of brain function-a result that may be due to chance.

Bacopa

Stough and colleagues (2001) suggest that B. monniera may improve higher order cognitive processes that are critically dependent on the input of information from our environment such as learning and memory. [96]

Extracts of Ginkgo biloba and Bacopa monniera have been shown to produce positive effects on cognitive function in healthy subjects, being antioxidant properties and cholinergic modulation the main cause. However, Nathan and colleagues (2004) found that extracts of Ginkgo biloba and Bacopa monniera had no cognitive enhancing effects in healthy subjects. [97]

The results show a significant effect of the Brahmi on a test for the retention of new information, but the rate of learning was unaffected, suggesting that Brahmi decreases the rate of forgetting of newly acquired information. Tasks assessing attention, verbal and visual short-term memory and the retrieval of pre-experimental knowledge were unaffected. Questionnaire measures of everyday memory function and anxiety levels were also unaffected. [98]

Bacopa monnieri failed to improve mental function in studies. This type of inconsistency suggests that the limited benefits seen in some studies were due to chance. [99]

Choline

Choline is widespread in the foods we eat. The average diet provides about 500 to 1,000 mg of choline per day. 2,4 Lecithin, a fatty constituent in foods, is a major source of choline; it is comprised mostly of a type of choline called phosphatidylcholine (PC).

For some people, adequate choline supplies cannot be maintained by other nutrients, and must be obtained independently through diet or supplements. Choline and folate share methylation pathways. Robert and colleagues 1999 in a study found that choline is utilized as a methyl donor when folate intake is low, and the synthesis of phosphatidylcholine is insufficient to maintain choline status when intakes of folate and choline are low. The authors call for a dietary choline of > 250 mg/d to maintain plasma choline and phosphatidylcholine when folate intake is low. [100]

Huperzine A, a cholinesterase inhibitor, is derived from the Chinese herb Huperzia serrata. According to Dana Belongia of Georgetown University in Washington, products based on huperzine A have never been tested on memory or other brain functions in healthy adults, and there have been no controlled clinical trials outside China assessing its toxicity and efficacy. [91]

DMAE

There are no studies looking at DMAE's impact on memory or powers of concentration in healthy adults. DMAE has failed nearly every test concerning neurological diseases like Alzheimer's and Huntington's chorea. [91]

Phosphatidylserine (PS)

According to FDA very limited and preliminary scientific research suggests that phosphatidylserine may reduce the risk of dementia and the risk of cognitive dysfunction in the elderly. FDA concludes that there is little scientific evidence supporting these claims. [101]

Lipoic acid

According to study of Dana Consortium, treatment of HIV patients with thioctic acid, also known as alpha-lipoic acid did not improve cognitive function. According to this study thioctic acid has no benefit. [102]

Folic acid

According to Durga and colleagues low folate and raised homocysteine concentrations in blood are associated with poor cognitive performance in the general population. The authors found, as part of the Dutch FACIT trial that folic acid supplementation for 3 years significantly improved domains of cognitive function that tend to decline with age. [103]

Martha Morris of the Rush Institute for Healthy Aging in Chicago says that this study is not relevant to people in USA because US grain supply is fortified with folate whereas European supply is not, and the Dutch volunteers lacked folate at the beginning of the trial. [91]

Folate reduces incidence of depression in man but not in women [104]

According to Simon Gilbody and colleagues low folate has been linked to depression, but research is contradictory. In a meta-analysis the researchers found significant relationship between folate status and depression. Folate levels were also lower in depression. The authors concluded that there is accumulating evidence that low folate status is associated with depression.

Kentaro Murakami and colleagues in a study in Japan found that higher dietary intake of folate was associated with a lower prevalence of depressive symptoms in Japanese men but not women. In this study no significant association with depression was observed for the intake of riboflavin, pyridoxine, cobalamin, total omega 3 PUFAs, alfa linolenic acid, eicosapentaenoic acid, or docosahexaenoic acid in man and woman. The authors call for more research on this topic. They stress that there are hypotheses that omega-3 PUFA may have an important role in neurotransmitter synthesis, degradation, release, reuptake, and binding, resulting in a pattern of neurotransmitter activity that has been associated with depression [105]

Ginkgo biloba

Kennedy and colleagues 2007 assessed the effects of a low dose of GBE alone and complexed with the soy-derived phospholipids such as phosphatidylserine and phosphatidylcholine to enhances the bio-availability.

No improved performance was found with 120 mg of GBE alone. Enhancement following GBE complexed with phosphatidylcholine resulted in modest cognitive enhancement, but GBE complexed with phosphatidylserine resulted in significantly increased speed of memory task performance. The authors conclude that complexation with phosphatidylserine appears to potentiate the cognitive effects associated with a low dose of GBE and call for further research. [106]

Vinpocetine

Vinpocetine is a semi-synthetic derivative of vincamine. Vincamine is an alkaloid derived from the plant Vinca minor L. Vinpocetine, as well as vincamine, are used in Europe, Japan and Mexico as pharmaceutical agents for the treatment of cerebrovascular and cognitive disorders, and in the United States it is marketed as a dietary supplement as cognition enhancer. [107]

Another study concerning the vinca alkaloid called vinconate was published in 1997 suggesting the alkaloid as possible cognition enhancer.[108] However, Schardt says that only preliminary studies exist dated 15 years ago, asessing vinpocetine for treatment of stroke or Alzheimer's disease. [91]

According to a study published in 1989 fifteen Alzheimer's patients were treated with vinpocetine in a trial during a one-year period. Vinpocetine failed to improve cognition on psychometric testing or overall functioning. The authors concluded that vinpocetine is ineffective in improving cognitive deficits and does not slow the rate of decline in individuals with Alzheimer's disease. [109]

n-3 PUFAs and depressed mood

According to Appleton and colleagues 2006 trial evidence that examines the effects of n-3 PUFAs on depressed mood is limited and present considerable heterogeneity. The evidence available provides little support for the use of n-3 PUFAs to improve depressed mood. [110]

Supplementation with n-3 fatty acids reduce cancer risk of esophagus [111]

Samir P. Mehtan and colleagues in a study published in 2008 found that supplementation with EPA significantly changed n-3 fatty acid concentrations and reduced COX-2 concentrations in human lower esophagus, reducing the risk of cancer. Population with a high consumption of fish and consequently, n-3 fatty acids had been found to have a reduced risk of esophageal adenocarcinoma.

The researchers believe that the suppression of eicosanoid production through inhibition of cyclooxygenase 2 (COX-2) resulting from high intake of eicosapentaenoic acid (EPA) is responsible for a reduction of risc of the disease.

The controversity of fibre and colorectal cancer

The legend of dietary fibre

[112] The British surgeon Denis Burkit, working in an hospital in Uganda, developed the theory that Dietary fibre could reduce the colorectal cancer risk and other diseases, because Africans consumed more fruit and vegetables as found in western diet. As a tribute to his outstanding contributions in the fields of medicine, nutrition and health the Kellogg Company of Great Britain Limited initiated the Denis Burkitt Study Awards in 1994.

In an article in Zeit Wissen 5, 2006 Eva-Maria Schnurr looks at the evolution of the theory of dietary fibre and colorectal cancer. In the 80s bran was added to cereals, yoghurt and even beverages in the hope to reduce risk of colorectal cancer. This theory is not being maintained any more by many scientists. According to the article from Eva-Maria Schnurr the English scientist Burkit, developing the initial theory of fibre to reduce colorectal cancer did not consider the age of the people he considered for his work, most of them died so early that no cancer could show up. [113]

Doubts about the theory came up due to the findings of a series of researches on this matter:

Wheat Bran fibre Trial [114]

Alberts and colleagues 2000 found in the Wheat Bran fibre Trial that a dietary supplement of wheat-bran fibre (of 13,5 g fibre in two to three cups of cereal per day) does not protect against recurrent colorectal adenomas.

Polyp Prevention Trial [115]

According to their authors, the Polyp Prevention Trial provided no evidence that adopting a low-fat, high-fibre fruit- and vegetable-enriched eating plan reduces the incidence of colorectal cancer.

The position of the National Institutes of Health related to dietary fibre [116]

The National Institutes of Health in a release comments the findings of the Wheat Bran Fibre Trial and the Polyp Prevention Trial:
"The results provided no evidence that the particular dietary interventions employed (i.e., a low-fat, high-fibre, high-fruit and -vegetable eating plan or a high-fibre cereal supplement) in the particular population studied (individuals who had had one or more polyps removed at colonoscopy) were effective in preventing the recurrence of polyps. However, overall evidence suggests that a low-fat, high-fruit and - vegetable, high-fibre diet has benefit in reducing the risk of many chronic diseases - heart disease, hypertension, obesity, diabetes, and others. This trial specifically looked at the effect of diet on the growth of new colorectal polyps in people who had already had a polyp removed. A healthy diet does not replace the need for people with a history of polyps to have regular checkups. "

Wheat-bran fibre does not protect against colorectal adenomas [117]

Jacobs and colleagues 2006 assessed the epidemiologic evidence that cereal fibre protects against colorectal cancer is equivocal, with a supplementation of 13.5 g per day of wheat-bran fibre to reduce the rate of recurrence of colorectal adenomas. The authors found that a dietary supplement of wheat-bran fibre does not protect against recurrent colorectal adenomas.

The Women's Health Initiative (WHI) found no link between reduction of colorectal cancer and high fruit, vegetables and whole grain intake [118]

The clinical trials of the Women's Health Initiative (WHI) were designed to test the effects of postmenopausal hormone therapy, diet modification, and calcium and vitamin D supplements on heart disease, fractures, and breast and colorectal cancer.

The WHI trial also reported no link between a diet low in fat, and high in fruit, vegetables and whole-grain intake. This study was restricted to women and appears to agree with the results from Arizona.

The Women's Health Initiative (WHI) found no link between supplementation of calcium and vitamin D and reduction of colorectal cancer [119]

Higher intake of calcium and vitamin D has been associated with a reduced risk of colorectal cancer in epidemiologic studies and polyp recurrence in polyp-prevention trials. However, randomized-trial evidence that calcium with vitamin D supplementation is beneficial in the primary prevention of colorectal cancer is lacking.

However, the authors conclude that daily supplementation of calcium with vitamin D for seven years had no effect on the incidence of colorectal cancer among postmenopausal women. The long latency associated with the development of colorectal cancer, along with the seven-year duration of the trial, may have contributed to this null finding. Ongoing follow-up will assess the longer-term effect of this intervention.

Vitamin D3 and calcium supplementation reduces all-cancer risk in women [120]

Joan M. Lappe and colleagues in a study of supplementation of 1,400-1,500 mg calcium and 1,100 IU vitamin D3 over 4 years the calcium/vitamin D3 group experienced a 60 per cent decrease in their cancer risk compared to the group taking placebos, but did not change significantly for the group receiving only calcium.

The authors concluded that mproving calcium and vitamin D nutritional status substantially reduces all-cancer risk in postmenopausal women.

Fibre and resistant starch [121]

Soluble Fiber

(e.g., pectins, gums, mucillages, and some hemicellulose) - Soluble fiber is found in fresh and dried fruit, vegetables, oats, legumes and seeds.

Insoluble fibre

(e.g., cellulose, lignin and hemicellulose) - Insoluble fiber is found in the plant cell walls of whole grain bread, whole grain cereals, fruits, vegetables, unprocessed bran and wheat germ. Many insoluble fibres, including cellulose and psyllium, are not fermented.

Resistant Starch

- Starch that resists digestion is found in foods such as legumes, bananas (especially under-ripe, slightly green bananas), and unprocessed whole grains. Resistant starch incorporates some benefits of insoluble fibre as well as soluble fibre, and acts like dietary fibre.

There are four types of resistant starches:

- RS1

Physically inaccessible or digestible resistant starch, such as that found in seeds or legumes and unprocessed whole grains.

- RS2

Resistant starch that occurs in its natural granular form, such as uncooked potato, green banana flour and high amylose corn.

- RS3

Resistant starch that is formed when starch-containing foods are cooked and cooled such as in bread, cornflakes and cooked-and-chilled potatoes or retrograded high amylose corn.

- RS4

Starches that have been chemically modified to resist digestion, and are not found in nature.

Improved gluten free breads [122]

Coeliac disease demands for gluten free foods. Starches from corn, rice, soy and buckwheat flours in stead of wheat flour. However, according to Jaraslaw Korus and colleagues 2008, these products lack important nutrients and dietary fibre.

To improve the weaker structure of gluten-free bread compared with conventional bread and to increase its content of dietary fibre Korus replaced partially corn starch in gluten free bread with resistant starch, aiding functioning of the digestive tract, microbial flora, blood cholesterol levels and can help in diabetes management.

On the other hand, preparations using resistant starch are "less prone to pasting". Since the structure of bread depends on starch gelatinisation, it was thought that this could affect loaf quality.

The gluten free breads containing corn starch, potato starch, guar gum, pectin, freeze dried yeast, sucrose, salt, plant oil and water was modified in that 10, 15, 20 and 50 per cent of corn starch was replaced by corn resistant starch, and the same proportions of potato starch were replaced by tapioca resistant starch.

The best results in lowering the hardness of the bread were obtained with tapioca resistant starch, however, other effects on rheological parameters, such as crumb texture were limited.

The authors concluded that partial replacement if starch in recipes for gluten free bread with resistant starch preparation doesn't significantly influence organoleptic quality, but the breads with resistant starch were seen to have much high dietary fibre content, as well as insoluble and soluble fractions. A total dietary fibre of 6.30g per 100g had been achieved, which makes it advisable for practice.

Physical properties and biological impact of resistant starches RS3 [123]

According to Haralampu retrograded starch, and particularly retrograded amylose RS3, are the most thermally stable forms.

Early studies on the digestibility stated that retrograded amylose was non-nutritive, a slow digestion by amylases, however, were recently discovered, releasing glucose and other oligosaccharides.

The author stresses that the use of resistant starch in food products for certain target groups, such as diabetics and athletes should be considered. Haralampu reviews sources of resistant starches highly concentrated in retrograde amylose and describes a product for modulating the glucose response of diabetics, and effects on an extruded cereal product.

Wheat Bran fibre Trial and the Polyp Prevention combined suggest benefit of fibre for men, but not women [124]

Elisabeth Jacobs and colleagues 2006 combined the Wheat Bran fibre Trial and the Polyp Prevention Trial, Both studies separately presented no link between dietary fibre and the risk of colon cancer, but pooled together a benefit of fibre was noted for men, but not women.

According to Jacobs the conflicting results from other studies can be explained by the difference in benefits between the sexes.

Warning about too much fibre intake [125]

According to Goodlad the benefits of fibre have been attributed to its binding to bile acids but fibre can also bind various other harmful materials. Vegetable fibre has several times more galactose than cereal fibre and this high galactose content will inhibit binding of mitogenic galactose binding lectins, such as peanut agglutinin, which has been shown to stimulate cell proliferation in the human colon. Goodlad concludes that fermentable fibre and resistant starch can give origin to colorectal adenomes.

Increases in tumour in rats following supplementation with fibre-like substrates such as resistant starch have also been reported. Williamson and colleagues 1999 conclude that it is possible that any increased risk posed by resistant starch is restricted to carriers of germline mutations in APC (adenomatous polyposis (Apc) gene). [126] [127]

Another theory says that soluble fibre and excessive cereal fibre are being added to probiotic and functional foods as well as drinks by the producers trying to profit from a new wave toward high fibre foods. This may lead to a negative health effect as excessive fibre may lead to gas which can drive bacteria back to the small intestine where they may cause erosion of the gut.

Goodlad reinforces the advice that fibre is still an important aspect of a diet and in the diet fibre should come from fibre-rich food such as fruits and vegetables and less so from cereals, to have a balanced diet and everything in moderation,and that exercise and avoiding obesity is important.

The Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School Report 1999 [128]

Fuchs and colleagues 1999 found no association between the intake of dietary fibre itself and the risk of colorectal cancer. The researchers measured the contributions of dietary fibre from cereals, fruits, and vegetables.

Only fruit fibre was associated with an appreciable but not significant reduction in risk. In contrast, greater consumption of vegetable fibre was associated with a small increase in the risk of colorectal cancer.

Nurses' Health Studie found no link between Fibre and colon cancer [129]

Nurses' Health Studie in USA observed 76 947 nurses starting in 1976 over 16 years. And the Nurses' Healt Study II started in 1989 could not find a link between dietary fibre and colorectal cancer.

Limitations of Studies [130]

The validity of the results were questioned on account of the poor compliance with the dietary intervention in the WHI trial. Limitations of the wheat bran Fibre and the polyp prevention trial had a follow- up period of only two to four years, ting into consideration that the latency period of the cancer is between 10 and 20 years. Another limitation with this new-pooled analysis is the use of polyps, as a marker for actual cancer.

Total dietary fibre does not protect against colorectal cancer, but whole grain does [131]

In 2007 Schatzkin and colleagues found in a large prospective cohort study, that total dietary fibre intake was not associated with colorectal cancer risk, whereas whole-grain consumption was associated with a modest reduced risk.The association with whole grain was stronger for rectal than for colon cancer.

Dietary fibre and Risk of Colorectal Cancer in the Japan Collaborative Cohort Study [132]

Wakai and colleagues 2007 found no differences in the strength of associations with the risk between water-soluble and insoluble dietary fibre. For food sources of fibre, bean fibre intake was somewhat inversely correlated with colorectal cancer risk.

This might point to the findings that soluble fibres from fruit and vegetable have shown to be protective towards colorectal cancer and insoluble cereal fibre tends to increase the risk of cancer in humans.

The authors concluded that dietary fibre my be protective against colorectal cancer, mainly against colon cancer, however, the role of dietary fibre in the prevention of colorectal cancer seems to remain inconsistent, and further investigations in various populations are being suggested by the authors.

The weak point of the Women's Health Initiative [133]

Martinez and Jacobs in an editorial in 2007 point out that most prospective studies of colorectal cancer and calcium intake suggests a threshold effect in that risk reduction is seen at intakes of approximately 600-1000 mg/day, with no further protection beyond these levels.

These findings might explain the null effects observed in the Women's Health Initiative, in which women received a total calcium intake of approximately 2150 mg/day, levels that, based on the prospective data, are consistent with no effect. Martinez and Jacobs rise again the question of whether calcium supplementation could protect individuals with low or moderately low baseline intakes of calcium.

Matinez and Jacobs also note that according to Grau and colleagues 2007 [134] the protective effect of calcium supplementation for colorectal adenoma recurrence extends as long as 5 years after cessation of supplementation and that this effect is slightly stronger than that observed during the intervention phase.

Calcium supplementation reduces the risc of colon cancer [135]

Dr. Baron and colleagues of The The Calcium Polyp Prevention Study Group conducted a randomized, double-blind trial of the effect of supplementation with 3 g calcium carbonate carbonate (1200 mg of elemental calcium daily) on the recurrence of colorectal adenomas. The authors found that Calcium supplementation is associated with a moderate reduction in the risk of recurrent colorectal adenomas.

No direct relation between calcium supplementation and colon cancer explained [136]

Weingarten, Zalmanovici and Yaphe 2008 reviewing the literature found two studies which suggest that there may be a moderate protective effect for dietary supplementation of at least 1200mg elemental calcium per day on the development of colorectal adenomatous polyps. The authors stress, however, that a direct relationship of an effect of calcium supplementation on colorectal cancer itself was not given.

Low calcium to magnesium ratio may reduce colorectal cancer risk [137]

Dr. Qi Dai presented the result of the Calcium Polyp Prevention Study in November 2008. According to the author the supplementation of 1,000 mg calcium daily for 4 years was found to have a moderate effect to prevent colorectal adenoma recurrence in subjects with a low calcium to magnesium intake ratio.

The study says that the protective effect occurred only if the dietary ratio of calcium to magnesium intake was low before treatment and remained low during treatment. The authors suggests the use of a personalized ratio of calcium/magnesium ratio rather than supplementing with only one or the other alone.

Sphingadienes of soy may become a new therapy for colon cancer [138]

Dr. Julie Saba and colleagues 2009 found a class of substances called sphingadienes in the fruit fly. Sphingadienes are also present in soy. According to the authors sphingadienes are natural lipid molecules which promote the deaths of cancer cells. Sphingolipid metabolites regulate cell proliferation, migration, and stress responses and alterations of their metabolism may induce carcinogenesis, cancer progression, and drug resistance. Sphingadienes were found to block Akt translocation from the cytosol to the membrane causing the death of cancer cells. The authors conclude that these sphingadienes of soy may become a new therapeutic of cancer.

Sphingolipids comprise a complex group of lipids concentrated in membrane rafts. Their metabolites function as signaling molecules. Sphingolipids were found by Saba and colleagues in 2008 in the fruit fly Drosophila. They contained two double bonds in the long chain base of either 14 or 16 carbons with conjugated double bonds at C4,6. The Delta(4,6)-sphingadienes were found free , as phosphorylated , and as the sphingoid base in ceramides. The authors suggest that these lipids may contribute to the muscle degeneration in Drosophila Sply mutans. [139]

Schmelz 2004 report that sphingolipids are lipid messengers in the signaling pathways of growth factors, cytokines, cellular stresses and others and cell death. Schmelz assessed the mechanisms sphingolipids utilize in the prevention of cancer in early carcinogenesis. [140]

Dietary factors and sphingomyelin [141]

Sphingomyelin metabolism envolve anticancer signals such as ceramide and sphingosine. Ateration of this metabolism is linked to various forms of cancer, especially colon cancer. Duan 2004, therefore, describes the sphingomyelin metabolism pathway and their link to colon cancer and stresses the dietary factors that affect the metabolism of sphingomyelin and may protect from colon cancer.

Sphingomyelin occurs in modest amounts in the diet, in sloughed mucosal cells, and in bile. It is digested by the mucosal enzymes alkaline sphingomyelinase and ceramidase. In humans, alkaline sphingomyelinase is also secreted in bile. The digestion of sphingomyelin is slow and incomplete, which has been linked to the inhibition of cholesterol absorption and colonic carcinogenesis. However, Fyrst and colleagues 2009 assessing diet containing milk sphingomyelin found that the increase in ileostomy content of ceramide plus sphingomyelin amounted to 19 per cent of the fed dose of sphingomyelin. The authoirs concluded that more than 81 per cent of dietary sphingomyelin is digested and absorbed by humans, and the level of sphingolipid metabolites may be influenced by diet. [142]

Influence of the colorectal cancer behavioural risk factors of individuals [143]

Individuals who were not adherent to screening reported having a greater number of risk factors than adherent individuals. Risk factors were considered in this study to be low physical activity, low fruit and vegetable intake, and low intake of multivitamins. The authors conclude that there is a need to develop interventions to modify the colorectal cancer behavioural risk factors that are common among screening-adherent and nonadherent individuals.

Prediction of the Spread of Colon Cancer [144]

Maode Lai and colleagues2010 identified two proteins (trefoil factor 3 and growth/differentiation factor 15) that occurred at significantly higher levels in the metastatic cells than in the primary colon cancer cells. This study may lead to a prediction of the spread of cancer cells after surgery. An earlier allowing treatment may be possible with this biomarkers blood test.

Heart drugs to fight colon cancer [145]

Cardiac glycosides, a family of naturally-derived drugs used to treat congestive heart failure and abnormal heart rhythms, were found useful in the treatment of colon cancer by Jenny Felth and colleagues 2009. The authors say that digitoxin in combionation with oxaliplatin exhibited synergism in treating the disease.

The European Prospective Investigation into Cancer and Nutrition (EPIC) study [143]

The European Prospective Investigation into Cancer and Nutrition (EPIC) study, found a very strong association between a high fibre intake and a reduction in the instance of colorectal cancer. People who ate more than 35 g of fibre a day had a 40 per cent reduced risk than those who consumed only 15 g. Colon cancer aetiology:

- The hypothesis that a diet high in fibre reduces colorectal cancer risk has been corroborated in the EPIC study. Our findings were published in parallel with the results from the PLCO cohort of the NIH-NCI. In that study, a similar protective effect of fibre on colorectal cancer polyps was observed. Together, these results indicate that fibre is protective both for the development of adenomatous polyps and for their malignant transformation.

- The hypotheses that consumption of red and processed meat increases colorectal cancer risk while intake of fish decreases risk is strongly supported by the EPIC results.

- The combination of these four dietary factors (i.e. fibre, fish, red and processed meats) plays a major role in colorectal cancer aetiology in addition to alcohol intake, obesity and low physical activity.

Summary of Scientific Activity on Colon Cancer in the EPIC Study [143]

Lancet 2003, Bingham and colleagues found an inverse relation of dietary fibre with colorectal cancer incidence with the greatest protective effect in the left colon, and least in the rectum. No food source of fibre is significantly more protective than others.

Bingham and colleagues 2004 confirmed the above findings after adjustment for folate and with a longer follow-up. (Cancer Epidemiol Biomarkers Prev 2004, Jenab et al: Higher nut and seed intake is not significantly associated to the risk of colorectal, colon, and rectal cancers in men but did show an inverse association with colon cancer in women.)

Greek EPIC study found moderate wine, little meat, many vegetables to be linked to longer life [146]

The largest effects on reduced mortality came from drinking moderate amounts of alcohol, eating little meat, eating lots of vegetables, eating fruits and nuts, and using olive oil. However, the individual components of the Mediterranean diet had an additive protective effect.

The authors stress the importance of overall diet being more important than individual components, with emphasis on moderate wine consumption during meals, preference for olive oil, low consumption of meat, and high consumption of vegetables, fruits, and legumes
The study of Trichpoulou and colleagues 2009 used data from the European Prospective Investigation into Cancer and Nutrition (EPIC) trial.

The contribution of each of the diet components to lower mortality were: moderate consumption of alcohol (23.5% of the effect), low consumption of meat (16.6%), high consumption of vegetables (16.2%), high consumption of fruits and nuts (11.2%), high monounsaturated-to-saturated lipid ratio (10.6%), and high consumption of legumes (9.7%).

The authors stress that eating lots of cereal products and few dairy products contributed to only 5% of the effect, and consumption of fish was associated with a nonsignificant increase in mortality.

The study supports the affirmations of other authors which say that it is not one single component of the Mediterranean diet that is driving reduced risk of mortality. Focusing on one food such as blueberries or folic acid supplements is not enough, but a healthy lifestile and a balanced diet like the Mediterranean diet is of importance.

The marketing of fibre

Dietary fibre components such as pectins, gums, cellulose and others, used as functional ingredients by the food industry are being used in marketing strategy to claim high fibre benefits.

Dietary fibre from cocoa suitable for low-calorie, high-fibre foodes preparations [147]

Elena Lecumberri and colleagues 2007 studied the composition and dietary fibre obtained from cocoa bean hus, a waste product from cocoa. This product contained 60.54% of total dry matter as dietary fibre, where 80% of these are insoluble fibre and 10 % are soluble dietary fibre and polyphenolic compounds (1.32% soluble polyphenols and 4.46% condensed tannins) The glucose retardation index of cocoa fibre were similar to other natural commercial insoluble fibres.

Dietary guidelines recommend a minimum daily intake of dietary fibre (DF) of 25 g (equivalent to 12.5 g dietary fibre per 1000 calories consumed), dietary fibre components like pectins, gums, cellulose and others have been used as functional ingredients.

The authors conclude that the antioxidant capacity of this fibre-rich cocoa powder and its physico-chemical properties render it a suitable product to be used in the preparation of low-calorie, high-fibre foods like chocolate cookies, chocolate cakes, dietetic chocolate supplements, etc. where the colour and flavour of this cocoa fibre might be advantageous.

The ACS Nutrition and Physical Activity Guidelines represent the most current scientific evidence related to dietary and activity patterns and cancer risk [148]

The consumer is made insecure by conflicting results of studies such as those commented above. Adherence to ACS Guidelines may clear the actual situation and provides a pattern to be followed. According to Kushi and colleagues 2006 the American Cancer Society (ACS) Nutrition and Physical Activity Guidelines are consistent with guidelines from the American Heart Association and the American Diabetes Association for the prevention of coronary heart disease and diabetes, as well as for general health promotion, as defined by the Department of Health and Human Services' 2005 Dietary Guidelines for Americans.

The ACS Guidelines include recommendations for individual choices regarding diet and physical activity patterns, but Kushi stresses that those choices occur within a community context that either facilitates or interferes with healthy behaviours.
The authors recommendation are therefore to develop a supportive social environment for individuals to choose healthy behaviours.

Physical activity relation to coronary heart disease [149]

Sattelmair et al 2011 assessed the relation between quantity of the specific amounts of physical activity required and the reduction of coronary heart disease. Previous studies showed only qualitative estimates such as low, moderate, and high physical activity.

Sattelmair and colleagues performed an aggregate data meta-analysis of related epidemiological studies. They found that 150 minutes of moderate-intensity exercise per week reduced the risk of coronary heart disease (CHD) by 14%, 300 minutes per week had a 20% lower risk of CHD, and 750 minutes per week of moderate intensity exercise had around a 25% reduction in risk of CHD compared with sedentary persons.

Physical activity lower than the minimum recommended amount by the 2008 US federal guidelines (150 Minutes/week) [150], also caused a significantly lower risk of coronary heart disease. Benefits of physical activity, particularly walking was generally associated with lower risks of total, ischemic, and hemorrhagic stroke among women than men, but more data are needed to support this affirmation. [151]

The study reinforce the US physical activity guidelines which say that some physical activity is better than none and additional benefits occur with more physical activity.

Supplements with vitamin B may be harmful [152]

It is known that folate deficiency induces DNA breaks and may alter cellular capacity for mutation and epigenetic methylation.

However, Schernhammer and colleagues 2007 found that supplements did not reduce the risk of cancer. B vitamins from multivitamin pills increased risk of developing pancreatic cancer by 139 per cent.

The mechanism of the different effect from vitamin from supplements and the effect of vitamins absorbed from food is unknown.

The authors suggest that the growth of a dormant tumor may be stimulated by folate and other similar vitamins, especially in case if a person with chronic shortage of these nutrients in his diet suddenly starts taking multivitamins in an effort to become healthy. Similar results have been found studying oestrogen-rich soy. Women eating soy all life long reduced the risk of breast cancer, but those who suddenly started to eat soy did increase the risk.

In this study nonusers of multivitamins were found to have a modest inverse trend between folate, PLP, and B12 and pancreatic cancer risk. This has not been observed among people using multivitamin supplement and among those who obtain these factors exclusively through dietary sources, there may be an inverse relation between vitamin B and the risk.

The author's advice is to maintain a normal weight and eat fruit and vegetables to avoid pancreatic cancer. Liver, wholegrain cereals, dairy products and green vegetables are good sources of B vitamins.

Folic acid increases the risk of some types of tumours [153]

Bernard Cole and colleagues 2007 found in a study that folate, when administered as folic acid for up to six years, does not decrease the risk of adenoma formation in the large intestine among individuals with previously removed adenomas. Another study by Schernhammer and colleagues 2007 (See www.ourfoo-news.com 03.06.2007: Supplements with vitamin B may be harmful) came to similar conclusion in relation to pancreatic cancer. [154]

In the study of Cole participants were randomly assigned to receive 1 mg/day of folic acid or placebo and to receive aspirin or placebo and were then examined three and six or eight years later. The researchers concluded that folic acid at 1 mg/d does not reduce colorectal adenoma risk. Further research is needed to investigate the possibility that folic acid supplementation might increase the risk of colorectal neoplasia.

Cornelia Ulrich and John Potter in an editorial said that folic acid promoted growth of carcinogenic lesions and calls of health professionals to rely carefully on multiagent chemoprevention and not to forget diet. [155]

The study of Schernhammer and the study of Cole may be a warning for excessive consumption of supplementation of the vitamin B group. Both studies call for more studies.

Mandatory fortification of certain foods with folic acid in the US and Canada were introduced in 1998 to reduce the incidence of pregnancies affected by neural tube defects.

Andrew Shao US dietary supplements industry association, the Council for Responsible Nutrition (CRN) says that the benefits of folic acid are well-documented, particularly in the area of reducing the risk of neural tube birth defect. There is also promising scientific evidence for folic acid in reducing the risk of congenital cardiovascular defects, stroke and Alzheimer's disease. [156]

Bioavailability and food safety of L pidolic acid salts [157]

According to the Scientific Panel AFC of the European Food Safety Authority, the bioavailability of calcium, iron, magnesium, potassium and zinc are absorbed from their L-pidolic acid salts is comparable to that from other water-soluble and dissociable salts permitted to be used in food supplements and foods intended for particular nutritional uses.

The use of calcium, iron, magnesium, potassium and zinc L-pidolic acid salts as source of these minerals for nutritional purposes to food supplements is of no safety concern at the maximum use levels of L-pidolic acid of 3 g/day.

Magnesium, calcium and zinc as L-lysinate in supplements were found safe by EFSA [158]

The European Food Safety Authority's Panel on Food Additives found Magnesium L-lysinate, calcium L-lysinate and zinc L-lysinate as sources for magnesium, calcium and zinc in supplements as safe.

The Panel says that a dose twice of what is found in normal diets is considered of no safety concern. The used supplements are salts of the amino acid L-lysine. L-Lysine, following ingestion, is absorbed and transported to the liver.

The Panel calculated that less than 9 g/day of lysine are ingested to provide a supplementation of 250 mg Mg/day, 800 mg Ca/day and 15 mg Zn/day. In a worst case assumption the Panel estimated the potential exposure to lysine to be up to 353 mg/kg bw/day for an adult with a standard body weight of 60 kg. These values are low compared to the level of lysine in protein rich foods.

Based on present data the Panel concluded that the use of magnesium L-lysinate, calcium L-lysinate and zinc L-lysinate used in food supplements as a source of respectively magnesium, calcium and zinc is not of safety concern at the proposed use levels.

Fortification of dairy products with magnesium [159]

According to Maud Cansell and colleagues about 20 per cent of the French population present a magnesium deficiency. Undersupply of this mineral has been linked to high blood pressure, cardiovascular diseases, muscular weakness, and diarrhoea.

The authors studied the supplementation of magnesium in foods like dairy products. Magnesium can induce in these foods chemical degradations, protein aggregation and generate an unpleasant taste. To avoid this the researchers created a blend of rapeseed oil, olive oil, olein, and/or miglyol. Polyglycerol polyricinoleate and sodium caseinate which traps the magnesium in the interior of a Water/Oil/Water emulsion. The unwanted reactions are avoided, and magnesium is released from the W/O/W emulsion by hydrolysis of the oil in the intestine. The emulsion is stable during pasteurisation.

Divalent ions decrease uptake of carotenoids [160]

Biehler et al 2011 stress that carotenoids, in order to become bioactive, require micellarization and intestinal uptake. Using an in vitro digestion model, the authors found that the divalent ions Ca and Mg and Zn and Fe reduced the necessary micellarization and cellular uptake of carotenoids of spinach. Fe and Zn presented the strongest inhibition.

However, the authors found an improved fractional cellular uptake from the micelles for all ions by up to 5-10 times, including neochrome (from neoxanthin) and luteoxanthin+auroxanthin (from violaxanthin). Divalent ions inhibition of carotenoid micellarization and uptake must be considered, when supplementation with these four ions take place.

Anti-inflammatory activity of green-lipped mussel extracts. [161] [162]

Treschow, together with Hodges and colleagues identified a family of omega-3 PUFAs which included C18:4, C19:4, C20:4, and C21:5 PUFAs in the green-lipped or green shell mussel Perna canaliculus. The C20:4 was the predominant PUFA in the extract, and was a structural isomer of arachidonic acid. These fatty acids presented significant anti-inflammatory activity in vitro.

According to the authors, the special configuration of the double bonds, located at positions 7, 11, 14 and 17, and two methylene groups positioned between the first and the second carbon atom inhibits the production of leukotriene and prostaglandin metabolites.

The authors suggest that the novel compounds may be biologically significant as anti inflammatory agents, due to their in vitro inhibition of lipoxygenase products.

Chronic inflammation may be linked to heart disease, osteoporosis, cognitive decline and Alzheimer's, and type-2 diabetes.

Some producers extract the oil from the dried mussel meat for specific uses. The fat free powder is then marketed as food supplement rich in glycosaminglycane, which is told to be a base substance for connective tissue and cartilage. Some suppliers complain that extracts without the lipid fractions and with less anti-inflammatory effect are cheaper than mussels with the oil fraction. They call for a correct labelling of the products which are degreased an those who are not.

Yeast extract under the influence of expanding bioethanol [163]

Increased cost of sugar molasses due to the European sugar reform, together with the increased use of bioethanol which reduces supplies available to the food ingredients industry, and high fossil fuel cost for energy used by industry for process, increase the price of yeast extract.

Yeast extract produced from sugar molasses by the yeast Saccharomyces cerevisiae, is increasingly being used in convenience foods as savoury ingredient and healthy ingredient as a substitute for salt and monosodium glutamate.

Fish oil supplementation improves large arterial elasticity [164]

Wang and colleagues 2007 found that a supplementation of 3 g fish oil during 8 weeks improved the large arterial elasticity (C1), but had no effect on blood pressure in overweight hypertensive patients. The elasticity of the small artery (C2),was not changed.

The authors conclude that fish oil supplementation can improve large arterial elasticity but has no effect on blood pressure. They call for more studies on this matter.

Docosahexaenoic acid (DHA) improves cognition in age-related cognitive decline (ARCD) and reduces the risk of Alzheimer disease [165]

The "Memory Improvement with Docosahexaenoic Acid Study" (MIDAS) by Yurko-Mauro and colleagues 2010 says that 6 month supplementation with 900 mg/d docosahexaenoic acid (DHA) may improve memory and learning in older adults with mild cognitive impairments.

The authors say that low DHA levels are associated with cognitive decline in healthy elderly and Alzheimer's patients, high DHA levels help reduce the risk of Alzheimer's disease. The MIDAS study focused on a population of healthy adults with age-associated memory impairment.

No benefit of DHA, however, in patients previously diagnosed with Alzheimer's disease [166]

Quinn and colleagues found in a study published in 2010 that DHA did not caused significant benefit on cognitive function in patients previously diagnosed with Alzheimer's disease. The authors stress that their results should not be applied to groups where DHA is administered before the disease apparent.

DHA supplements, and other dietary supplements should be taken over time and before a disease becomes notorius. Heathy nutritional habits should include a well-balanced diet, regular physical activity and dietary supplements may slow down ageing impairments, such as age-associated memory impairment.

Polysaccharides from brown marine algae as health benefits promising ingredient [167]

Seaweeds, such as Laminaria spp, are rich in polysaccharides which are classified as dietary fibres, because they are resistant to hydrolysis in the upper gastrointestinal tract. Human digestive enzymes did not hydrolyse laminarin, so this polysaccharide can be considered as a dietary fibre.

Laminarin is a beta-1,3-Glucan and function as a storage substance which can be compared to starch in plantson land. It is commonly obtained from the brown kelp alga Laminaria digitata. [168]

Alginates are currently used as low-cost thickening and viscosity stabilisers for such products as salad dressings, and for microencapsulated ingredients.

Isolation

Isolation of water insoluble laminarin-like polysaccharide has been achieved from Sargassum linifolium by extraction with hydrochloric acid and oxalic acid solutions, according to Abdel-Fattah and Hussein [169]. Devillé and colleagues found a hot HCl-based method as best strategy to isolate laminarin. [167]

Laminarin as imuno-stimulant agent

K H Kim and colleagues suggest that laminarin oligosaccharides and polysaccharides from Laminaria japonica, can be utilized to develop new immunopotentiating substances and functional alternative medicines [170].

Franck Hennequart and colleagues from the National University of Ireland in Galway, Health Sea International Symposium in Granville, Normandy in October. 2007. announced to have produced and identified four different extracts from the seaweeds, intended to be used in a range of drinks, including mineral water, orange juice and cold tea. According to Hennequart crude fucodians seem to demonstrate a prebiotic effect. The seaweed extracts were found to have anti-bacterial activity on some bacteria. Some of the extracts seem to have an anti-inflammatory effect. Tests on rats have shown no toxicological effects so far. [171]

Bioavailability of calcium from soymilk

Soymilk are often enriched with 120mg/100ml with calcium phosphate, calcium carbonate, or calcium chloride to obtain an equivalent content of calcium of cow milk. However poor solubility reduce bioavailability of calcium from soymilk.

Tang and colleagues 2007 found that fermentation of calcium-fortified soymilk with probiotic bacteria such as Lactobacillus acidophilus ATCC 4962 and L. casei ASCC 290 increased the calcium solubility up to 89 per cent, enhancing bioavailability. The low pH resulted from the production of lactic and acetic acid was found to cause the increased solubility.

The increase in calcium solubility observed was related to lowered pH associated with production of lactic and acetic acids. The conversion of the glucoside isoflavones into the bioactive isoflavone aglycone form was also observed.

The fermentation significantly increased also the conversion of isoflavones from their natural glucoside form into the biologically active aglycone forms such as diadzein, genistein and glycetein.

Disagreement between epidemiological/observational studies and randomised clinical trials [172]


Observational study

In statistics the goal of an observational study is to draw inferences about the possible effect of a treatment on subjects, where the assignment of subjects into a treated group versus a control group is outside the control of the investigator. This is in contrast with controlled experiments, such as randomized controlled trials, where each subject is randomly assigned to a treated group or a control group before the start of the treatment.

A major challenge in conducting observational studies is to draw inferences that are acceptably free from influences by overt biases, as well as to assess the influence of potential hidden biases. A bias is a prejudice in a general or specific sense, usually in the sense for having a preference to one particular point of view or ideological perspective. However, one is generally only said to be biased if one's powers of judgement are influenced by the biases one holds, to the extent that one's views could not be taken as being neutral or objective, but instead as subjective.

Observational studies serve a wide range of purposes, on a continuum from the discovery of new findings to the confirmation or refutation of previous finding. Some studies are essentially exploratory and raise interesting hypotheses. Others pursue clearly defined hypotheses in available data. In yet another type of studies, the collection of new data is planned carefully on the basis of an existing hypothesis. [173]

STROBE

In 2007, several prominent medical researchers issued the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement, in which they called for observational studies to conform to 22 criteria that would make their conclusions easier to understand and generalise. [173]

Randomized controlled trial (RCT)

A randomized controlled trial (RCT) is a type of scientific experiment most commonly used in testing healthcare services. 'RCTs are considered the most reliable form of scientific evidence in healthcare because they eliminate spurious causality and bias'. RCTs are mainly used in clinical studies, but are also employed in other sectors such as judicial, educational, and social research. involve the random allocation of different interventions (or treatments) to subjects. This ensures that known and unknown confounding factors are evenly distributed between treatment groups.

Traditionally the control in randomized controlled trials refers to studying a group of treated patients not in isolation but in comparison to other groups of patients, the control groups, who by not receiving the treatment under study give investigators important clues to the effectiveness of the treatment, its side effects, and the parameters that modify these effects.

Open trial

In an open trial, the researcher knows the full details of the treatment, and so does the patient. These trials are open to challenge for bias, and they do nothing to reduce the placebo effect. However, sometimes they are unavoidable, particularly in relation to surgical techniques, where it may not be possible or ethical to hide from the patient which treatment he or she received. Usually this kind of study design is used in bioequivalence studies.

Blind trials


Single-blind trial

In a single-blind trial, the researcher knows the details of the treatment but the patient does not. Because thepatient does not know which treatment is being administered (the new treatment or another treatment) there might be no placebo effect.


Double-blind trial

In a double bling trial, one researcher allocates a series of numbers to 'new treatment' or 'old treatment'. The second researcher is told the numbers, but not what they have been allocated to. Since the second researcher does not know, they cannot possibly tell the patient, directly or otherwise, and cannot give in to patient pressure to give them the new treatment. Therefore double-blind (or randomized) trials are preferred, as they tend to give the most accurate results.


Triple-blind trial

The most common meaning is that the subject, researcher and person administering the treatment are blinded to what is being given. Alternately, it may mean that the patient, researcher and statician are blinded.

Difficulties

A major difficulty in dealing with trial results comes from commercial, political and/or academic pressure. Most trials are expensive to run, and will be the result of significant previous research, which is itself not cheap. There may be a political issue at stake (compare or vested interests . In such cases there is great pressure to interpret results in a way which suits the viewer, and great care must be taken by researchers to maintain emphasis on clinical facts.

The Tatsioni analysis on disagreements between epidemiological/ observational studies and randomised clinical trials [174]

Athina Tatsioni and colleagues evaluated the citations for two highly cited observational studies for cardiovascular benefits associated with vitamin E supplementation and publications related to the protective effects of beta-carotene on cancer and estrogen on Alzheimer's disease They looked for an explanation how these benefits continue to be defended in literature, despite contradicting evidence from large RCTs.

In this trial despite the eventual accumulation of strongly refuting evidence, even in 2005, half of the articles citing these epidemiological studies were still favourable to the vitamin E claim.

The same situation was observed for beta-carotene, said the authors. "In 2006 more than half of the articles citing the highly cited epidemiologic articles on beta-carotene for cancer prevention remained favourable for these interventions.

The authors concluded that Claims from highly cited observational studies persist and continue to be supported in the medical literature despite strong contradictory evidence from randomized trials. According to the authors differential interpretation, inappropriate entrenchment of old information, lack of dissemination of newer data, or purposeful silencing of their existence is to be blamed for this situation. "

Controversity of results between observational and randomized clinical trials [175]

According to Andrew Shao, Ph.D., vice president, scientific and regulatory affairs, Council for Responsible Nutrition research may seem to contradict itself, however, that should not be interpreted to mean one type of study trumps another, particularly when different studies ask and answer different questions. Seemingly conflicting data can exist side by side, when one understands that not all studies are asking the same questions in the same populations.

Dr. Shao says "this suggests that researchers interpret research differently, depending on their bias and expertise. For pure scientific purposes, here's a valid hypothesis to test: conduct a trial on secondary prevention in heart patients with a lifetime of bad habits that likely contributed to their heart disease to determine if a nutrient might provide some benefit. But it's not valid to conclude from the results of that study that the nutrient doesn't work. We can't expect a simple vitamin supplement to reverse heart disease. So if that doesn't happen, we must interpret the results appropriately by placing the study in the proper context and acknowledge that the results don't answer the question of whether supplemental amounts of vitamin E in a healthy population could have prevented heart disease had it been used consistently over time in combination with other antioxidants."

Dr. Shao states, "The Randomized Clinical Trials RCTs with negative results attempted to answer the question, can a supplemental nutrient treat or reverse a disease or a lifetime of unhealthy habits in patients who are also taking prescription medications?"

The observational studies with positive results attempted to answer the question, "if we start with a mostly healthy population generally free of disease, can we identify various diet/nutrient and lifestyle factors that make them more or less prone to disease?"

"These are very different questions, making the studies incompatible for direct comparison and demonstrating that one type of study can't necessarily be used to refute the other. We firmly believe that RCTs should not be thought of as the only rigorous research approach. As the study authors point out, 'when randomized and observational studies disagree, it is incorrect to assume that nonrandomized studies are always wrong.' Rather, we should put studies into the appropriate context and evaluate the total body of evidence, which includes RCTs and observational studies, and other types of research."

The Chorane Study reinforces warning of antioxidants supplements [176]

The Cochrane study by Bjelakovic and colleagues was initially heavily criticised by the supplement industry, pointing out some errors. The authors published therefore a corrected version in JAMA (2008, Vol. 299, pp. 765-766).

The new version reinforces the conclusions of the original version writing that current evidence does not support the use of antioxidant supplements in the general population or in patients with certain diseases. Vitamin A, beta-carotene, and vitamin E may increase mortality. The authors call for more studies on beneficial and harmful effects on Vitamin C and selenium.

The authors stress further that antioxidant supplements need to be considered medicinal products and should undergo sufficient evaluation before marketing.

Antioxidant supplements for treatment of specific diseases, supplementation for specific needs of antioxidants, or the effects of antioxidants contained in fruits or vegetable were not assessed by the study. and more studies on this matter are needed.

Researcher recommend to be cautious in taking antioxidants [177]

Chronic reactive oxygen species (ROS) production by mitochondria may contribute to the development of insulin resistance, a primary feature of type 2 diabetes. Rieusset and colleagues 2008 report that high-fat, high-sucrose diet resulted in mitochondrial defects, insulin resistance and type 2 diabetes in rats. The authors explained that alterations in mitochondrial function were the result, and not the cause, of insulin resistance in mice. Their data suggest that chronic reactive oxygen species (ROS) production was the cause of the mitochondrial dysfunction, and antioxidants could avoid it. The authors concluded that treatment of diabetics with medications to block ROS production or its effects might may help conventional diabetes therapies. [178]

Dandona and colleaguies 2007 even state that caloric intake in the form of orange juice or fructose does not induce either oxidative or inflammatory stress, possibly due to antioxidant activity of flavonoids of the juice. [179]

However, Tiganis and colleagues 2009 say that physiological low levels of Chronic reactive oxygen species (ROS) may promote the insulin response and attenuate insulin resistance early in the progression of type 2 diabetes, prior to overt obesity and hyperglycemia.

The study lead by Tiganis found that mice lacking glutathione peroxidase 1 (Gpx1),an enzyme which eliminates ROS were protected against diabetes. The administration of antioxidants started the type 2 diabetes in these rats.

Tiganis says that antioxidants have negative effect in early type 2 diabetes and the development of insulin resistance. The increase of ROS may, under certain conditions, be helpful to avoid diabetes. However, it is necessary to determine when the effect of ROS are beneficial or become harmful. The authors suggest not to take daily antioxidant vitamins when there are no special indications to do so, and recommend exercise as a sound source of ROS.

Extract from red yeast Chinese rice Xuezhikang (XZK) reduced cardiovascular events and death [180]

David M. Capuzzi and colleagues 2008, report that treatment with XZK decreased CV and total mortality by 30% and 33%, the need for coronary revascularization by 1/3. According to the authors total and low-density lipoprotein cholesterol and triglycerides were lowered, and the good high-density lipoprotein cholesterol levels were raised. They concluded that long-term therapy with XZK decreased the recurrence of coronary events. New cardiovascular events and deaths were reduced. Xuezhikang is prepared from rice cultivated with the mold Monascus purpureus. The extract contains components of lovastatin, a drug which lowers bad cholesterol. The FDA isued a safety warning on red rice extracts due to its content of this drug.

FDA warning to avoid red yeast rice products [181]

The products are promoted as dietary supplements for treating high cholesterol. FDA says that side effects associated with lovastatin of red yeast rice are adverse interaction with other medications, it can cause severe muscle problems leading to kidney impairment. See the FDA warning at: http://www.fda.gov/bbs/topics/news/2007/new01678.html

Functional cheese with increased polyphenols [182]

Han and colleagues 2010 developed a functional cheese with 0.5 mg/ml single phenolic compounds, including catechin, epigallocatechin gallate (EGCG), tannic acid, homovanillic acid, hesperetin and flavones, and natural crude compounds, such as grape extract, green tea extract, and dehydrated cranberry powder in the cheese curd.

The authors report good retention of the added polyphenols. The gel-formation depended on the molecular properties and the hydrophobicity of the added phenolic compounds. Homovanillic and tannic acids reduced the pH of the cheese curd more that the natural crude compounds. The free radical-scavenging activity of the cheese was better than the effect of control cheese without added polyphenols.

Addition of polyphenols to different types of cheese, yoghurt, milk shakes or other dairy products may improve their quality and functionality, say the authors.

Development of functional ingredients and foods [183]

The market for functional ingredients and foods experiences a steadily growth resulting of healthier eating and lifestyle habits of the consumers. Day andd colleagues 2 009 stress the importance of functional ingredients not getting lost during the food processing, that they remain active and their bioavailability is guaranteed during storage. This should be tested before placing new bioactives and functional food ingredients on market. The authors present an approach of the development of functional ingredients and foods, using dermatan sulphate and black carrot concentrate as examples.

Nonmedical and medical literature often unreliable, says author [184]

Glisson and colleagues 2010 write that dietary supplements are not regulated by FDA and are often used as "alternative" or "complementary" therapy, leaded by subjective claims such as anticancer, anti-inflammatory, cardiovascular protection. Safety and possible effect have often never been assessed. Pharmacodynamic and pharmacokinetic data of dietary supplements are limited and of meager quality. Nonmedical literature related to dietary supplements are often of poor quality.

The authors advise physicians to take great care evaluating literature and advising patients, as even medical literature may present unreliable informations.

GMP for dietary supplements [185]

Melethil S 2006 stresses that the Dietary Supplement Health and Education Act (DSHEA) of October 1994 [186] ensures easier access to safe dietary supplements, which can be marketed without prior FDA approval; the burden is on this agency to show that a marketed dietary supplement is unsafe. However, FDA may issue regulations that require the manufacture to follow good manufacturing practice (GMP) standards to ensure their quality. The FDA in 2003 and 21007 proposed rules for GMP for the manufacture, packaging and storage of dietary supplements. [187]

Warning label on food supplements and tea containing ginger in Finnland [188]

EVIRA, the Finnish Food Safety Authority says there is reasons to limit the consumption of ginger products as well as the abundant or long-term consumption of ginger tea during pregnancy. A number of the chemical constituents of ginger could be harmful to foetal development; some of the chemical constituents have been found to cause e.g. cell mortality.

In order to protect consumers against health hazards Evira says that as long as the effect of ginger on the foetus is not clear, the following foodstuffs shall bear a separate warning label for pregnant women:
Food supplement containing ginger, ginger tea and corresponding drink powder must bear the following label: "Not recommended for pregnant women". Advertisements and other marketing efforts may not be targeted at pregnant mothers.

The known chemical constituents of ginger include e.g. zingiberen (30%), b-bisabolene (10-15%), sesquiphellandrene (15-20%), ar-curcumene, geranial, citronellol acetate and gingerols (approx. 5%).

Marcus and Snodgrass 2005 stress that the effect plant extracts are chemicals that have the same potential to cause serious adverse effects as found in conventional medicines. Rigorous scientific studies of the safety of dietary supplements during pregnancy are lacking. The authors urge obstetricians to advise women not to expose their fetuses to the risks of herbal medicines [189]

Researchers call for studies on the potential toxicity of ginger during pregnancy [190]

Chrubasik, Pittler and Roufogalis 2005 reviewed the pharmacological and clinical effects of ginger. Some antiemetic properties were found, however, clinical evidence beyond doubt is only available for pregnancy-related nausea and vomiting.

The authors stress that confirmatory study to exclude interaction of ginger preparations with platelet aggregation are needed. Pharmacokinetic data are only available for [6]-gingerol and zingiberene, and the potential toxicity should be monitored especially following ginger consumption over longer periods.

However, concerns remain about the effect of ginger on the fetus because of its uncertain mechanism of action. One proposed mechanism is inhibition of thromboxane synthetase, described in rat models, which has the potential to affect sex steroid differentiation of the fetal brain. [191]

Other studies found no safety risk of ginger use during pregnancy [191]

Portnoi and colleagues 2003 examined the safety of ginger use during pregnancy. The authors found no statistical differences in the outcomes between the ginger group and the comparison group with the exception of more infants weighing less than 2500 g in the comparison group. The authors concluded that ginger does not increase the risk of major malformations, and has a mild effect in the treatment of nausea and vomiting of pregnancy.

Borelli and colleagues 2005 assessed safety of ginger (Zingiber officinale) therapy for nausea and vomiting during pregnancy. The authors found no reports of adverse events during ginger treatment for nausea and vomiting in pregnancy, however, call for more studies to confirm the data on ginge safety. [192]

Phytate and phytic acid reduce the bioavailiability of micronutrients [193]

Rasmussen and colleagues 2008 describe phytate, phytic acid, phytase and its application in food and feed. The authors stress that phytic acid is the primary storage compound of phosphorus in seeds. Phytic acid strongly binds to metallic cations of Ca, Fe, K, Mg, Mn and Zn making them insoluble and thus unavailable as nutritional factors. This may be involved in worldwide nutrient deficiency of iron, zinc, and vitamin A.

Phytate is predominantly located in the aleurone layer (wheat, barley and rice) or in the embryo (maize). Phytic acid can be digested only by ruminants, because ot the microbes of their digestive system.

In developing countries plant foods are the major staples of the diet and the bioavailability of several micronutrients can be quite low. The authors stress that improving the nutritional value of this type of foods would improve the nutritional status of the entire population.

The first commercially available phytase was from Aspergillus niger , but now several phytases are on the market, from e.g., Peniophora lycii, Escherichia coli and Schizosaccharomyces pombe. Microbial phytases are better suited for industrial processes, because they have higher pH and thermal stability compared to plant phytases.

Production of phytase in transgenic plants using the Cauliflower Mosaic Virus (CaMV) 35S promoter resulted in enzymes similar to fungal phytase. Aspergillus fumigatus enzyme is also promising because it withstand the pelleting temperatures.

Phytase as feed additive and food products

Adding phytase in feed increases mineral, phosphorous and energy uptake in pig and broiler chicken. The use of phytase in breadmaking, in tofu and other soy-bean products is in discussion. Phytase of Aspergillus niger is of interest because it could work under acidic conditions of the stomach. Rasmussen and colleagues say, however, that exogenous phytase is only required for breadmaking when whole grains are used.

Bifidobacterium strains may improve wholegrain bread [194]

The consumption of wholegrain bread or fibre-enriched bread is increasing on regard of the benefits of a high-fibre diet, however, wholegrain foods are also seen to impair mineral absorption.

Monika Haros and colleagues 2009 used strains of bifidobacteria, such as B. infantis ATCC 15697 and B. pseudocatenulatum ATCC 27919 obtained from the American Type Culture Collection (ATCC), to reduce phytate and phytic acid levels in bread, because commercial phytases, used as feed additives, are not meant for human consumption.

Fermentation of the wholegrain bread with the Bifidobacterium strains reduced significantly phytic acid levels of myo-inositol hexaphosphate (InsP6) but did not remove the myo-inositol triphosphates (InsP3) which is beneficial to health.

The authors conclude that the use of bifidobacterium in wholegrain bread leavening may reduce the content of anti-nutrient compound phytate, resulting in a better absorption of minerals by the human gut.

Bifidobacterium promising probiotic to improve mineral absorption [195]

Probiotics are live organisms which present health benefits mainly in the gastrointestinal tract. Haros and colleagues 2009 suggest the use of the probiotic Bifidobacterium pseudocatenulatum to degrade phytate of wholegrain and fibre rich foods. The human strain, described by the authors, presented tolerance to bile as well as a selective adhesion capacity to human intestinal, similar to commercial probiotic B. lactis. The authors describe the degradation pathway of the myo-inositol hexaphosphate (InsP6) phytate by the B. pseudocatenulatum enzymes, and stress their probiotic contribution to the improvement of mineral absorption.

Various Bifidobacterium reducing the antinutritional properties of phytate [196]

Haro and colleaguies 2005 describe various Bifidobacterium spp. The authors wrote that B. globosum and B. pseudocatenulatum were optimally active at neutral-alkaline pH and B. adolescentis, B. angulatum and B. longum at acid pH. B. pseudocatenulatum showed the highest levels of phytase activity which dephosphorylate phytic acid (myo-inositol hexaphosphate, IP(6)) and generate several myo-inositol phosphate intermediates (IP(3)-IP(5)).

Fungal phytase as breadmaking improver [197]

Fungal phytase were used in the fermentation stage of the breadmaking of whole wheat bread by Haros and colleagues 2001. The possible use of phytase as a breadmaking improver has been tested in whole wheat breads by adding different amounts of fungal phytase. A considerable improvement of the bread characteristics were obtained.

Phytase addition activated the alpha-amylase, due to the release of calcium ions from calcium-phytate complexes. The authors concluded that the use of phytase in breadmaking improves the nutritional value of the bread and presents the advantages of activating endogenous alpha-amylase.

Unsafe bleaching agent in flour [198]

China daily reports that some flour bleaching agents contain as much as 30 percent pulverized lime, a substance linked to gradual damage to the lungs and eventually the entire respiratory system. Pulverized lime was added to the bleaching agent to achieve low selling prices by the Yuzhong Food Additive Company in Rugao in East China's Jiangsu province.

The bleaching agent used in flour production is usually a blend of benzoyl peroxide (BPO) and corn flour. Experts say the use of lime is forbidden in flour production, because there are no regulations which allows its use, but no clear regulations exist. Benzoyl peroxide is one of the most important organic peroxides to improve flour.

A social problem

Chen Junshi, of the national food safety and risk assessment committee, points out that the use of unregulated additives in food production is unavoidable in the current peasant population.

Allowed flour bleaching agents [199]

Bread improvers and other bakery ingredients are used to make the bread white, soft and get the the dough optimized for industrial production lines.

Flour bleaching agent is a food additive added to flour in order to make it appear whiter (freshly milled flour is yellowish) and to oxidize the surfaces of the flour grains and help with developing of gluten.

Usual bleaching agents

Usual bleaching agents are organic peroxides, namely benzoyl peroxide, calcium peroxide, nitrogen dioxide, chlorine, chlorine dioxide (which is reported to produce diabetes-causing contaminant alloxan when reacting with the proteins contained in flour), Azodicarbonamide. Use of chlorine, bromates, and peroxides is not allowed in the European Union. Flours treated with bleaches and improving agents generally show higher loaf volume and finer grain.

The oxygen from air bleaches flour while it ages during storage. Chemical bleaching, however reduces the transit time and reduces costs.

Flour bleaching agents

Flour bleaching agents are added to flour in order to make it appear whiter (freshly milled flour is yellowish) and to oxidize the surfaces of the flour grains and help with developing of gluten.

Maturing agents

Maturing agents are added to flour in order to help with gluten development. They may or may not also act as bleaching agents. Common maturing agents are various flour bleaching agents, azodicarbonamide (E927), carbamide (E927b), potassium bromate (E924), (acts as a bleaching agent in USA), ascorbic acid (helps form gluten), phosphates, malted barley.

Processing agents

Processing agents help with various aspects of handling the dough during baking. L-cysteine (E920, E921, quantities in the tens of ppm range help soften the dough and thus reduce processing time)

The bromate, after reacting with the yellow compounds in the flour, is converted into harmless bromide. Chlorine dioxide is a gas that dissipates, so there is none of that left in the flour either. Any excess of benzoyl peroxide would (theoretically) decompose as soon as the flour is heated.

Dough conditioners [200]

Dough conditioners contain emulsifiers, such as DATEM (Diacetyl tartaric acids)Ester of Monoglyceride) and calcium stearoyl-2-lactylate, to increasing water absorption and gluten strength. Other dough conditioners are:
Calcium carbonate or monocalcium phosphate adjust water hardness and pH. Calcium carbonate increases both water hardness and pH; monocalcium phosphate increases water hardness and decreases pH.

Potassium bromate, ascorbic acid, potassium iodate, and azodicarbonamide (ADA), are maturing agents which improve gluten strength.

Ammonium salts improve yeast fermentation.
Amylase and other enzymes are used to improve yeast fermentation and browning, and to delay staling.

Dough conditioners are used to get dough better handled in automated equipment. Dough conditioners are added to frozen doughs to avoid damage of the gluten structure. Dough conditioners also reduce mixing and fermentation time.

Not allowed in the EU

Potassium bromate, azodicarbonamide, calcium peroxide, benzoyl peroxide.

Natural bleaching agents [201]

Roozen and colleagues 1993 looked for natural bleaching agents. Teey report that native soya flour contains at least 3 lipoxygenase isoenzymes, which improve dough characteristics by peroxidizing unsaturated fatty acids followed by oxidation of proteins and carotenoids, improving rheology and bleaching of the dough. Their data suggest that bread improvers containing enzyme active soya flour were more resistant to storage in form of powder compared with a paste type.

The Brazilian oil fruit pequi has antiinflamatori effects and may reduce blood pressure [202]

The oil of the Brazilian pequi (Caryocar brasiliense Camb.) is mostly composed of oleic and palmitic fatty acids and may alter the ratio of triglyceride to cholesterol in postprandial lipidemia. Ana L. Miranda-Vilela and coleagues 2009 found further that pequi oil could reduce exercise-induced inflammation and blood pressure, and modulate postprandial lipidemia in runners older than 45 years. The authors stress that pequi oil may become a valuable supplement for athletes.

Pequi pulp is a very popular food in some parts of Brazil eaten by itself raw or prepared or used as an ingredient in cooking or to flavor beverages. Pequi with rice and chicken is especially popular among locals.

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