# Metabolomics/Applications/Nutrition/Non-Nutrient Chemicals

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Non-Nutrient Chemicals

## Introduction to Non-Nutrient Chemicals

A nutrient is defined as a substance that an organism must obtain from its surroundings for growth characterization that was used for food components that could be measured were just labeled nutrients. But if they were not nutrients, they could still be neatly classified as anti-nutrients, toxicants, or just interesting non-nutrients. Of course, components are not so simply characterized these days.
Currently non-nutrient chemicals are substances that are found in food that could potentially affect human health but are not identified as nutrients. Non- nutrients can be found in food as texture and food physico-chemistry, color, taste or smell. It is important to have an understanding that the chemical components of each non nutrient determines it physical properties. It is these different characteristics that really determine any possible effects they may have on human health.
Studies investigating several commonly consumed non-nutrient chemicals have shown that dietary consumption of particular chemicals can aid in the prevention of common metabolic disease states, such as obesity and diabetes. Dietary isoflavones and catechins can serve as inhibitors of intestinal absorption of free radicals and excess lipid buildup. Isoflavones are extensively present in Asian diets, and there is also a greater consumption of catechins (found in green tea) in the Asian population. The Asian population also has a smaller rate of cardiovascular disease, which may be connected with consumption of the aforementioned chemicals.
Nutritional supplements such as glucosamine and melatonin have been found to improve injury recovery and sleep cycle disorders, respectively. Both substances are naturally occurring in the body, but may be present in larger quantities with few adverse effects. Other studies use the effect of high fat diets on mice to watch for genomic biomarkers that indicate susceptibility to insulin resistance, obesity, and other cardiovascular risk factors. While most of the studies are inconclusive as to the extent of these benefits, there is a strong positive correlation between regular consumption of anti-oxidants and reduced risk factors for cardiovascular diseases.

## The bioavailability of non-nutrient plant factors: dietary flavonoids and phyto-oestrogens

One of the best-studied non-nutrient chemicals is quercetin, a flavonoid that is a member of the flavonol subgroup. Quercetin is not vital to human health, but has been shown to affect it, qualifying it as a non-nutrient chemical (NNC). Quercetin has been shown to exist in significant quantities in many common foods, including onions, French beans, apples, apricots, cherries, grapes, wine, and tea, both green and black. To get an idea of how significantly quercetin affects human metabolism, its bioavailability was measured. Unsupplemented test subjects were found to have quercetin concentrations in a range of 0.5-1.6 µM in their plasma. Further testing was conducted to determine the degree to which the quercetin was metabolized. This lead to the discovery that quercetin is extensively metabolized by humans; less than 1.5% of ingested quercetin excreted in urine had an intact flavonoid structure. The fact that human plasma contains quercetin begs the question, “How does quercetin affect humans?” The Zutphen Elderly Study has shown that quercetin intake is significantly inversely associated with coronary heart disease. This study also provided evidence that flavonoids may protect against stroke. The study found that dietary intake of flavonoid was inversely associated with stroke incidence. Flavonoids have long been known for their antioxidant properties, and so it not surprising that researchers suspect that this may be the cause for its health benefits. Oxidative damage to LDL is considered to be an important stage in the development of atherosclerosis. Knowing this, researchers examined quercetin’s ability to inhibit the in vitro oxidative modification of LDL, and found that the concentration of quercetin found in plasma (0.2 µM) is capable of inhibiting this effect by up to 50%. Further research is underway to find out if this process is actually occurring in humans
Quercetin:
http://upload.wikimedia.org/wikipedia/commons/9/90/Quercetin.png
New Terms

### Bioavailability

    The degree to which or rate at which a drug or other substance is absorbed or becomes available at the site of physiological activity after administration. (Dictionary.com)

### Flavonoid

    The term flavonoid (or bioflavonoid) refers to a class of plant secondary metabolites, known for their antioxidant activity. (Wikipedia.org)
Citation:
Wiseman, Helen. "The bioavailability of non-nutrient plant factors: dietary flavonoids and phyto-oestrogens." Proceedings of the Nutrition Society 58.01 (1999): 139-146. 12 Feb. 2009 <http://journals.cambridge.org/download.php?file=%2FPNS%2FPNS58_01%2FS002966519900021Xa.pdf&code=0cf9d3502db30778a467b20ce538f628>.

## Effects of metabolites of the lignans enterolactone and enterodiol on osteoblastic differentiation of MG-63 cells.

Metabolites made by certain plant derivatives have been studied for the effects they could potentially have in aiding human health. Lignans are chemicals groups readily found in plants, they are converted into phytoestrogens by microorganism found in your intestines. Due to the fact that lignans are a not essential to maintain the human health, but are shown to be able to affect it they are classified as non-nutrient chemicals.
The most commonly studied phytoestrogens are those derived from isoflavones, meanwhile the lignan phytoestrogens are recently being noticed. Lignans are being looked at because of the role they could potentially play in Osteoporosis. Specifically plant-derived lignans are converted into enterolactone and enterodiol in the colon. Osteoblasts play an important role in the bones; their differentiation affects the strength and rigidity of the bones. This study wanted to determine the effects enterolactone and enterodiol had on the development of osteoblasts. To assay any affect these lignan phytoestrogens had on osteoblasts scientists needed to find a human like osteoblast cell line (MG-63). The cell line was grown in the presence of enterolactone and enterodiol in order to test the effects of the phytoestrogens on cell viability, alkaline phosphotase (ALP) activity, transcriptional level of osteonectin, and collagen I. The study determined that enterolactone and enterodiol had biphasic effects on the cells. This means that at low dosages the phytoestrogens acted as stimulators but at high dosages they completely inhibited any activity. Further research is being done to determine any potential anti-tumor effects phytoestrogens might have.
http://commons.wikimedia.org/wiki/File:Enterodiol_and_Enterlactone.svg
New Terms
Biphasic: having two phases (Merriam-Webster.com)
Phytoestrogens: a diverse group of naturally occurring non-steroidal plant compounds that, because of their structural similarity with estradiol (17β-estradiol), have the ability to cause estrogenic or/and antiestrogenic effects (Wikipedia.org)
Citations: · Jie Feng, Zhongli Shi and Zhaoming Ye, “Effects of Metabolites of the Lignans Enterolactone and Enterodiol on Osteoblastic Differentiation of MG-63 Cells”, Biol. Pharm. Bull., Vol. 31, 1067-1070 (2008) .J-STAGE [Japan Science and Technology Information Aggregator,Electronic] E-Journal. 19 Jan. 2008. 10 Feb. 2009 <http://www.jstage.jst.go.jp/article/bpb/31/6/31_1067/_article>.
· "biphasic." Merriam-Webster Online Dictionary. 2009. Merriam-Webster Online. 10 February 2009 http://www.merriam-webster.com/dictionary/biphasic

## First Experimental Demonstration of the Multipotential Carcinogenic Effects of Aspartame Administered in the Feed to Sprague-Dawley Rats

Morando Soffritti, Fiorella Belpoggi, Davide Degli Esposti, Luca Lambertini, Eva Tibaldi, and Anna Rigano
Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1392232
Main Focus:
This article is a scientific research study that is examining the carcinogenic effects of Aspartame, a common artificial sweetener, when administered to healthy Sprague-Dawley Rats. This research highlights the potential effects of non-nutrient synthetic chemicals can have on mammalian cells.
http://commons.wikimedia.org/wiki/File:Aspartame_structure.png
Key Terms:
Aspartame (AMP) is a widely used artificial sweetener used in place of sucrose in soft drinks. It is currently the second most commonly used artificial sweetener used.
Histopathology is the study and examination of biological tissues for diseases.
Lymphoma is a type of cancer that infects the Lymphocyte population of the immune system. (http://www.emedicinehealth.com/lymphoma/article_em.htm)
Leukemia is a malignant cancer of the bone marrow and blood. It is characterized by the uncontrolled accumulation of blood cells and proliferation. (http://www.leukemia-lymphoma.org/all_page?item_id=7026) Necropsy is a term analogous to autopsy, or postmortem examination. (http://www.medterms.com/script/main/art.asp?articlekey=4513)
Summary:
This laboratory research examines the effects of synthetic non-nutrient chemicals that may be absorbed in the human diet. Aspartame, as a widely used artificial sweetener, is often found in a variety of soft drinks and other beverages in place of natural sucrose. Because the metabolic effects of aspartame and other artificial compounds are not completely understood, there is always a possibility for undesirable effects. In this particular study, researchers examined the toxicity and carcinogenicity in a mammalian system of Sprague-Dawley Rats. Researchers examined the long term effects of frequent bioassay of aspartame in various concentrations, over life span. Rats were fed with aspartame supplemented water, until death, rodents then underwent complete necrocropsy for examination of cancers.
As results of this study, the researchers found an increased incidence of malignant tumors and myelomas. Researchers found a high incidence of lymphomas and leukemia in female rats, which they concluded due to the direct metabolite of aspartame, formaldehyde which is the same metabolite that occurs in human metabolism of aspartame.
In conclusion the researchers responsible for this study found Aspartame to have high potential for multiple types of cancers, even at low daily doses. It is predicted that the results of this study could in fact be a large predictor as to the potential carcinogenic effects of aspartame in humans.

## Non-Nutrient Food Functions

http://apjcn.nhri.org.tw/server/MarkWpapers/BookChapters/B081x.pdf
The functions of non-nutrients found in food as texture, food physico-chemistry, color, taste or smell. For the same chemical composition food may have a completely different physico-chemical property. To some extent the ability of food to assume such different characteristics depends on the presence of certain components, like dietary fiber, its amount and type could change the texture of a certain food.
Although the color of foods is usually just written off as insignificant, it might also have biological effect on humans other than making food look more attractive. Substances such as lycopene, which is responsible for giving tomato its brilliant color has been ignored because it is not a Vitamin A precursor even though it’s a caratenoid. Except recently they have linked lycopene with being a powerful antioxidant, which can prevent tissue damage done by oxygen radicals. For taste or smell coffee is a good example of to the level of which a collection of volatile substances can form during roasting. Fufuryl and pyrrole type compounds form the aroma that is released from roasting coffee. It is of high interest to know that if these compounds are in the coffee drink itself or just simply the aroma that is released, there are compounds that could be opiate receptor ligands. It is also known there are lipid- rich coffee fractions other than caffeine, which could elevate LDL cholesterol and triglycerides in humans. A table of non nutrients of physiological importance defined chemically as well as a table with the physiological effects these non-nutrients would have within a system.
New Terms

### Physico-chemistry (physical chemistry)

    The natural science dealing with the relationship between chemical and physical properties of matter.
(http://medical-dictionary.thefreedictionary.com/Physicochemistry)

### pharmacology

    the study of drug action (Wikipedia.org)
Course Relevance This is relevant to the course because it is important to understand that the chemical composition of a certain chemical can affect the way it works during a metabolic process.
Relevance to Articles Talks about the phytochemicals that are extensively found in many food sources and are usually have antioxidative properties.

## Non- Nutrients

http://www.solae.com/soybasics/nutritionbasics/necessarynutrients/nonnutrients.jsp
Main Focus:
The main purpose of this source is to identify the different types of Non- nutrients that could be found in an individuals diet. The substances listed on this source are the supplements found in food that affect human health but are not classified as necessary nutrients.
Summary:
This website describes the functions, dietary allowance, toxicity and common food source of fiber, choline and phytochemicals. Fiber is any indigestible complex carbohydrate that is usually found in fruits, oat, legumes and barley. There is no recommended allowance of fiber and an individual cannot suffer from fiber deficiency. Fiber is not toxic but eating a diet high in fiber could lead to intestinal discomfort from excessive gas formation.
Choline is made within the human body from the amino acid methionine, but some is ingested through diet. It is involved in the synthesis of neurotransmitters acetylcholine, and lecithin. Even though choline is not considered a nutrient an adequate amount of it should be made in the body in order for neurons to function properly. The website has a chart which indicates the amounts that should be ingested depending on age of the individual. High doses of choline could lead to low blood pressure and mild liver damage. Choline is usually found in dairy products, soybeans, broccoli and other sources. Phytochemicals’ effects on human health are still being studied but many of the different chemicals and their sources are listed on a table in the website.
New Terms
Recommended Dietary Allowances (RDA), the daily dietary intake level of a nutrient considered sufficient to meet the requirements of nearly all (97–98%) healthy individuals in each life-stage and gender group. (Wikipedia.org)
diverticulum (plural: diverticula) is medical or biological term for an out pouching of a hollow (or a fluid filled) structure in the body. (Wikipedia.org)
Course Relevance
This is applicable to the class because it discusses the different non essential substances found in food that could potentially affect human metabolic processes.
Relevance to Articles
It explains in details the different non-nutrients that can be present in a persons diet. It also talks about the amounts that a person can take without it having adverse effects on their health.

## Food Additives

Main Focus: The main purpose of this website is to educate people about common chemicals and additives used during food processing and manufacturing. Created by The Center for Science in The Public Interest, this website does an excellent job in presenting health information of some of these popular chemicals in a coherent and easy to understand manner. This includes lists of compounds that are safe for consumption as well as including information on chemical compounds that people should watch for or abstain from.
Key Terms: Chelating Agents are chemicals used to prevent the binding of metal ions. These are used in the food manufacturing process to prevent metal-catalyzed oxidative breakdown; used to preserve flavor, freshness, and color. (http://www.dow.com/versene/app/food/) An Emulsifier is a chemical used to bind or mix two immiscible fluids, such as water and oil.
A Thickening Agent is a chemical used to increase viscosity in liquid compounds, often used in cooking to add texture and stabilize mixture. An Artificial Sweetener is a chemical additive that alone supplies no taste but once combined with certain foods produces a desirable taste.
Summary: This website is arranged in a large table format, displaying nearly 100 different natural and synthetic compounds used in food process and manufacturing. Utilizing icons and a table format, this user-friendly site enables readers to easily access potentially harmful chemical additives with ease of access. This website advises readers to whether a compound is safe, cautious, harmful or even banned for consumption in a diet. This list describes many synthetic non-nutrient compounds that are found in food as well as some naturally derived. This list is predominately non-nutrient compounds that are added to foods that supply either taste or manufacturing benefits through their use.
Course Relevance
It is relevant to the course because it helps identify how the certain chemical properties of a substance can affect human health.
Relevance to the Articles
It talks about food artificial sweetener, which is what one of the articles is about.

## Key Piece to Prostate Cancer Puzzle Found

The study of non-nutrient chemicals (NNCs) is a new technique in the world of research. The number of chemicals found in food that are not vital to human health far outnumber the number of compounds that are. Furthermore, the evidence that these NNCs affect human health is proliferating. It is not surprising then to find that more and more research is being aimed at understanding these NNCs, and how exactly each of them affects human health. Using these new techniques, scientists from the University of Michigan have found that the level of sarcosine, an amino acid derivative, in the urine of prostate cancer patients is an indicator of the type of tumor that patient is inflicted with. Research has shown that benign cancer cells, when exposed to sarcosine, become aggressive and multiply rapidly. Furthermore, it has been shown that if aggressive cancer cells are deprived of sarcosine, inhibition of replication resulted. This finding is among the first to result from the new field of metabolomics. Already it has been found that there are at least ten metabolites present in cancerous prostate cells that are not found in healthy prostate cells. Expanding our knowledge of NNCs and their affect on the many varieties of tissue found in humans seems to be a promising way to expand our knowledge of human health. Though a long way off, scientists hope to be able to monitor metabolite content in human tissue and interpret how these levels affect health.
New Terms

### Sarcosine

    The N-methyl derivative of glycine. It is naturally found in muscles as well as other body tissue. (Wikipedia.org)
http://upload.wikimedia.org/wikipedia/commons/c/c0/Sarcosine.png
Citation: DeNoon, Daniel J., and Louise Chang. "Key Piece to Prostate Cancer Puzzle Found:

## Green Tea as Inhibitor of Intestinal Absorption of Lipids: Potential Mechanism for its Lipid Lowering Effect

    http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1852441&tool=pmcentrez

### Main Focus

    This paper describes how catechins in green tea inhibit absorption of lipids in the intestine.

### New Terms
#### Epigallocatechin gallate

    the ester of epigallocatechin and gallic acid and a type of catechin, and an antioxidant (http://en.wikipedia.org/wiki/Epigallocatechin_gallate)

#### Emulsion

    a mixture of two or more immiscible (unblendable) liquids (http://en.wikipedia.org/wiki/Emulsifier)

#### Catechin

    polyphenolic antioxidant plant metabolites, belonging to the flavonoid family (http://en.wikipedia.org/wiki/Catechins)

#### Chylomicrons

    large lipoprotein particles that transport dietary lipids from the intestines to other locations in the body. (http://en.wikipedia.org/wiki/Chylomicron)

#### Antioxidant

    a molecule capable of slowing or preventing the oxidation (electron transfer) of other molecules. Oxidation reactions can produce free radicals, which can damage cells. (http://en.wikipedia.org/wiki/Chylomicron)

### General Overview

    Green tea has long been suggested as a health drink due to its anti-oxidant properties. Studies now show that green tea catechins minimize the absorption of dietary fat, cholesterol, and other lipids. This is because one of the major catechins present in green tea, epigallocatechin gallate (EGCG), inhibits intestinal absorption. It is likely that catechins from green tea could be used in the future to treat those at risk of cardiovascular diseases.
    Studies have shown an inverse risk between hypertension and green tea consumption. It is debatable whether this reduced risk is due to LDL cholesterol oxidation or the antioxidant properties of green tea, but the outcome remains the same. The lipid lowering ability appears to be due to the poor absorption of catechins in the intestines. Although they appear to inhibit lipid absorption, catechins are not as effective at inhibiting fat absorption, because fat absorption is dependent on the types of fat that are present.
    Catechins alter the properties of a lipid emulsion, decreasing hydrolysis of fat. EGCG also appears to interfere with the uptake of lipids, particularly extremely hydrophobic lipids, such as cholesterol. It does not appear to affect less hydrophobic lipids. EGCG has been shown to precipitate cholesterol from bile salt solution, but it does not affect solubility of fatty acids. It is theorized that catechins from green tea interact with transporters on the brush border membrane, influencing up take of cholesterol and other lipids. This especially the case in intestinal lumen cells. Catechins may also influence steps involved in the assembly and secretion of chylomicrons, which transport LDL and VDL cholesterols.
    Further studies will need to be conducted to determine the mechanism of catechin induced inhibition of lipid absorption, but thus far it is evident that green tea and catechins reduce the intestinal absorption of lipids. ECCG appears to be the most adept at inhibition, due to its ability to form complexes with lipids and lypoitic enzymes, thus inhibiting absorption processes. Also of interest for future studies would be the exploration of whether catechins interfere with non-nutrient lipophilic compounds that are naturally found in the environment. Such compounds can be toxic, and catechins provide a potential dietary means of reducing the absorption of such compounds.

### Course Relevance

    This demonstrates an additional treatment for individuals with high cholesterol and other health/metabolic problems that could minimize drug interactions.

## Phylometabonomic Patterns of Adaptation to High Fat Diet Feeding in Inbred Mice

    http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2244706

### Main Focus

    This paper discusses different molecular biomarkers indicative of environmental stressors which can trigger metabolic diseases.

### New Terms
#### Hyperinsulinemia

    presence of abnormally high concentrations of insulin in the blood (http://www.merriam-webster.com/medical/insulinemia)

#### Biomarkers

    indicator of a particular disease state or particular state of an organism (http://en.wikipedia.org/wiki/Chylomicron)

#### Hyperglycemia

    a condition in which an excessive amount of glucose circulates in the blood plasma (http://en.wikipedia.org/wiki/Hyperglycemia)

#### Plasma

    is the yellow liquid component of blood, in which the blood cells are suspended (http://en.wikipedia.org/wiki/Blood_plasma)

#### Adiposity

    adipose tissue or body fat or just fat is loose connective tissue composed of adipocytes. Adipose tissue is derived from lipoblasts. Its main role is to store energy in the form of fat, although it also cushions and insulates the body. (http://en.wikipedia.org/wiki/Adiposity)

### Summary

    Rodent models have been invaluable in researching the phenomenon of insulin resistance and characterizing the physiological and molecular mechanisms involved in the progression of cardiovascular diseases such as diabetes and obesity. High fat diet is used to induce these disease states in model organisms, and is used to observe the metablomic and physiological impact that results from the progression of insulin resistance and obesity.
    Five different types of inbred mice were placed on a high-fat diet (HFD) for 3 weeks at 5 weeks of age. Each strain was evaluated through a series of tests to detemine HFD effect on phenotypes, insulin regulation, and glucose homeostasis.
    The BALB/c strain was the only strain to exhibit increased food energy consumption on the HFD. 3 weeks of HFD feeding generally induced hyperglycemia and hyperinsulinemia, however, in three of the strains examined (DBA/2, BALB/c, and 129S6), HFD feeding had little effect on glucose tolerance or intolerance, suggesting that those strains are insulin resistant. Relationships between phenotypes were investigated according individual correlations. The highest correlations were between glucose tolerance data vs. insulin secretion and adiposity indices vs. plasma triglyceride levels. Correlations between blood lipids, BMI, and insulin secretion were only found in the fat fed group. This study demonstrated that that transgenomic efforts result strain specific changes in the abundance of metabolites processed by gut microflora, which may contribute to fatty liver predisposition, predisposition to high cholesterol levels, and are therefore directly relevant to disease susceptibility
    Integrating metabonomic-profiling data from the HFD mice and the control mice allowed for the identification of predictive biomarkers associated with specific cardiovascular disease states. In the example used in the paper, altered metabolism of choline and lipids creates a strong susceptibility to diet induced obesity, diabetes and fatty liver diseases. These biomarkers could serve as potential drug targets for further studies, or as potential genetic tests to predict susceptibility to cardiovascular diseases.

### Course Relevance

    This particular paper is demonstrating practical applications of systems biology to metabolic conditions. Metabolic diseases are typically triggered by a variety of stressors (environment, diet, etc), and this paper demonstrates potential molecular markers to evaluate those most at risk for cardiovascular disease. We evaluate some of the reasons why metabolic diseases occur and the pathways involved in the Metabolism course.

## Dietary isoflavones in the prevention of cardiovascular disease: A molecular perspective

    http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T6P-4P40KSN-1&_user=47004&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000005018&_version=1&_urlVersion=0&_userid=47004&md5=9ff7846efe0041ad5112c01696576d6f

### Main Focus

    This journal article discusses research conducted on the ability of soy isoflavones to reduce factors that can contribute to the development of cardiovascular disease, specifically the isoflavone genistein and its effects on glutathione peroxidase and NO production.

### Key Terms
#### Isoflavones

    a class of organic compounds, often naturally occurring, related to the flavonoids. Many act as phytoestrogens in mammals. Being polyphenols, they are antioxidants. http://en.wikipedia.org/wiki/Isoflavone

#### Genistein

    an isoflavone found primarily in soy that functions as an antioxidant and interacts with estrogen receptors. http://en.wikipedia.org/wiki/Genistein

#### Estrogens

    steroid compounds, named for their importance in the estrous cycle, and functioning as the primary female sex hormone. http://en.wikipedia.org/wiki/Estrogen

#### Endothelium

    the thin layer of cells that line the interior surface of blood vessels. http://en.wikipedia.org/wiki/Endothelium

#### Andioxidant

    a molecule capable of slowing or preventing the oxidation of other molecules. http://en.wikipedia.org/wiki/Antioxidant

#### Radical

    atoms, molecules or ions with unpaired electrons on an otherwise open shell configuration. http://en.wikipedia.org/wiki/Free_radical

#### Glutathione peroxidase

    the general name of an enzyme family with peroxidase activity whose main biological role is to protect the organism from oxidative damage. http://en.wikipedia.org/wiki/Glutathione_peroxidase

#### LDL

    a type of lipoprotein that transports cholesterol and triglycerides from the liver to peripheral tissues. http://en.wikipedia.org/wiki/Ldl_cholesterol

#### Nitric oxide (NO)

    an important messenger molecule involved in many physiological and pathological processes within the mammalian body both beneficial and detrimental. http://en.wikipedia.org/wiki/Nitric_oxide

### Summary

    This journal article opens with a discussion of nutrigenomics, which is a section of this Wikibook. For more information about nutrigenomics, see (link to Wikibook page).
    Isoflavones are non-nutrient plant compounds found mainly in soybeans. Isoflavone supplements are available that are derived from Chinese clover. Major forms of soy isoflavones include genistein, diadzein, and glycitein. Genistein is the most prominent isoflavone in soy-based foods and supplements. Unprocessed soybeans have an isoflavone content of approximately 1.2-4.2mg isoflavone per gram of plant material. Legumes contain a small amount of isoflavones, as well as currants and raisins. Other fruits and vegetables have very small amounts of isoflavones. Soybean pods (Edamame)are a rich source of isoflavones
    Depending on how soy products are processed, isoflavone levels can vary greatly. First generation soy foods like soy flour and texturized vegetable protein contain a greater amount of isoflavones than seond generation products like tofu yogurt and tempeh burger. Heat can cause changes in the chemical forms of isoflavones. In Asia, daily isoflavone consumption is about 20-50mg, but in Western countries intakes are under 1mg per day. Westerners can take commercial isoflavone supplements to increase intake.
    Isoflavones are very similar to mammalian estrogen and bind to estrogen receptors. This binding can initiate effects similar to estrogen in the body. Isoflavones might affect estrogen receptors on different types of tissues in specific ways. For example, they might have more effect on coronary vessels than endometrium. Soy isoflavones have much lesser affinity for the receptors than mammalian estrogen, however.
    Isoflavones also have antioxidant properties that can affect gene expression. They may also be able to suppress some tumor formation, scavenge radicals, and chelate metals. The isoflavone genistein can protect endothelial cells from damage and increase the expression and activity of glutathione peroxidase.
    Nutrigenomic studies have been conducted on the cardiovascular effects of isoflavones. Increased isoflavones in the Asian diet may lower the incidence of cardiovascular disease in Asian populations compared with the West. Isoflavones have been proposed to reduce LDL cholesterol, modulate pro-inflammatory cytokines, and improve vascular reactivity among other effects. Genistein may inhibit cardiovascular problems by triggering the modification of transcription of genes involved in the process. It affects the expression of genes encoding for proteins involved in vascular tone and proteins that enhance endothelial NO production. Synergistic interactions between the genes involved in NO production and vascular tone may reduce blood pressure.

### Relevance to class material

    In class we discuss glutathione as well as cholesterol and cholesterol-related diseases.

## Nutrition Supplements: Vitamins, Minerals, and Non-Nutrient Supplements

http://www.bidmc.org/YourHealth/HolisticHealth/AlternativeTherapies.aspx?ChunkID=37436

### Main Focus

This Web Site covers the basics of nutrition supplements. Links to database articles cover three specific non-nutrient supplements (isoflavones, glucosamine, and melatonin) in greater depth.

### Key terms
#### Megadosing

    the administration of large doses of vitamins to combat conditions considered wholly or in part due to their deficiency. http://encyclopedia.farlex.com/Megadosing

#### Isoflavone

    a class of organic compounds, often naturally occurring, related to the flavonoids, many of which act as phytoestrogens in mammals. http://en.wikipedia.org/wiki/Isoflavone

#### Phytoestrogen

    a diverse group of naturally occurring non steroidal plant compounds that, because of their structural similarity with estradiol (17-β-estradiol), have the ability to cause estrogenic or/and antiestrogenic effects. http://en.wikipedia.org/wiki/Phytoestrogen

#### Glucosamine

    an amino sugar and a prominent precursor in the biochemical synthesis of glycosylated proteins and lipids. http://en.wikipedia.org/wiki/Glucosamine

#### Melatonin

    a naturally occurring hormone found in most animals, including humans, and some other living organisms, including algae, which is important in the regulation of the circadian rhythms of several biological functions including sleep. http://en.wikipedia.org/wiki/Melatonin

#### Pineal gland

    a small endocrine gland in the vertebrate brain. http://en.wikipedia.org/wiki/Pineal_gland

#### Irritable bowel syndrome

    a blanket term for a variety of diseases causing discomfort in the gastro-intestinal tract. http://en.wikipedia.org/wiki/Irritable_bowel_syndrome

### Summary

    Vitamin and mineral supplements first became widely available for use in the 1930s. In the 1960s, “megadose” therapy became popular. Megadosing involves taking more than that needed amount of a vitamin, mineral, or non-nutritive chemical in order to produce a specific health benefit. There are certain risks and benefits involved in this practice. Also common is the practice of taking the daily value of a supplement as “nutrition insurance,” in case it is not obtained through diet. Three different non-nutritive supplements are discussed in the content of this web site: isoflavones, glucosamine, and melatonin.
    Isoflavones are water-soluble chemicals found in soy as well as other plant sources that have shown some potential anti-cancer benefits as well as reducing risk factors for heart disease. Many isoflavones are phytoestrogens—plant chemicals that have a similar effect on the body as estrogen. Isoflavones bind to estrogen receptors in the body and illicit an effect similar to estrogen but to a lesser degree. These chemicals can block “real” estrogen from taking effect by blocking the binding sites. This could potentially benefit those at risk for diseases linked to an over-production of estrogen like breast and uterine cancer. Isoflavones can reduce the overall level of real estrogen in the body by tricking it into thinking that it already has enough.
    In addition to reducing cardiovascular risk factors, isoflavones have been shown to reduce menopausal symptoms, osteoporosis, and to reduce the appearance of fine wrinkles. Also, they may improve the effectiveness of in-vitro fertilization. Double blind studies looking into these proposed health benefits have had mixed results. Overall the results are inconclusive. Isoflavone supplementation is generally safe, but can alter menstrual cycle and have an impact on fetal development in high doses. The therapeutic dosage for isoflavones is considered to be 40 to 80mg daily, while the average daily dietary intake in Japan is around 28mg.
    A bottled melatonin supplement available in drugstores Glucosamine is a substance found in gristle and the shellfish that is often used for the treatment of osteoarthritis. It is produced naturally by the body to make cartilage. Glucosamine is an amino sugar derived from glucose—one oxygen atom is replaced by a nitrogen.
    Glucosamine supplementation is used by atheletes for joint and tendon injuries and may improve symptoms of rheumatoid arthritis in addition to its use for osteoarthritis. Glucosamine supplements are available in three different varieties: glucosamine sulfate, glucosamine hydrochloride, and N-acetyl glucosamine. Studies suggest that all three may be equally effective. The therapeutic dosage is 500mg taken three times daily. Like isoflavones, studies are inconclusive concerning the health benefits of this supplement. Although it is generally considered not to have any adverse effects, some people may be allergic to the supplement.
    Finally, melatonin is a hormone that is often used to treat sleep disorders and interrupted sleep cycles. Melatonin is also produced naturally by the body to regulate sleep patterns. The pineal gland is stimulated to produce melatonin when it is dark. Studies have shown that melatonin is effective for travelers who suffer from jet lag and insomnia patients. Preliminary studies also suggest possible benefits for irritable bowel syndrome. Dosage of melatonin is suggested at 1 to 5mg taken half an hour before bedtime. Safety precautions should be taken because it can cause drowsiness up to two hours after taking the supplement. Due to its mechanism, it is not suggested for patients with depression, schizophrenia, or autoimmune diseases. Safe maximum dosages have not been established.

### Relevance to the class

    We have studied the molecule glucose, from which glucosamine is derived. Also, we will cover hormones to some extent, which isoflavones mimic.

# Articles for future review as Metabolism class assignments
### Influence of acute phytochemical intake on human urinary metabolomic profiles
#### Main Focus

       Identify the main focus of the resource. Possible answers include specific organisms, database design, intergration of information, but there are many more possibilities as well.
Reviewer: Seana C

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#### Summary

       Enter your article summary here. Please note that the punctuation is critical at the start (and sometimes at the end) of each entry. It should be 300-500 words. What are the main points of the article? What questions were they trying to answer? Did they find a clear answer? If so, what was it? If not, what did they find or what ideas are in tension in their findings?

#### Relevance to a Traditional Metabolism Course

       Enter a 100-150 word description of how the material in this article connects to a traditional metabolism course. Does the article relate to particular pathways (e.g., glycolysis, the citric acid cycle, steroid synthesis, etc.) or to regulatory mechanisms, energetics, location, integration of pathways? Does it talk about new analytical approaches or ideas? Does the article show connections to the human genome project (or other genome projects)?

### Phylometabonomic Patterns of Adaptation to High Fat Diet Feeding in Inbred Mice
#### Main Focus

       Identify the main focus of the resource. Possible answers include specific organisms, database design, intergration of information, but there are many more possibilities as well.
Jordan C

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#### Summary

       Enter your article summary here. Please note that the punctuation is critical at the start (and sometimes at the end) of each entry. It should be 300-500 words. What are the main points of the article? What questions were they trying to answer? Did they find a clear answer? If so, what was it? If not, what did they find or what ideas are in tension in their findings?

#### Relevance to a Traditional Metabolism Course

       Enter a 100-150 word description of how the material in this article connects to a traditional metabolism course. Does the article relate to particular pathways (e.g., glycolysis, the citric acid cycle, steroid synthesis, etc.) or to regulatory mechanisms, energetics, location, integration of pathways? Does it talk about new analytical approaches or ideas? Does the article show connections to the human genome project (or other genome projects)?

### Green Tea as Inhibitor of the Intestinal Absorption of Lipids: Potential Mechanism for its Lipid-Lowering Effect
#### Main Focus

       Identify the main focus of the resource. Possible answers include specific organisms, database design, intergration of information, but there are many more possibilities as well.

#### New Terms
##### New Term 1

    Definition. (source: http://)

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#### Summary

       Enter your article summary here. Please note that the punctuation is critical at the start (and sometimes at the end) of each entry. It should be 300-500 words. What are the main points of the article? What questions were they trying to answer? Did they find a clear answer? If so, what was it? If not, what did they find or what ideas are in tension in their findings?

#### Relevance to a Traditional Metabolism Course

       Enter a 100-150 word description of how the material in this article connects to a traditional metabolism course. Does the article relate to particular pathways (e.g., glycolysis, the citric acid cycle, steroid synthesis, etc.) or to regulatory mechanisms, energetics, location, integration of pathways? Does it talk about new analytical approaches or ideas? Does the article show connections to the human genome project (or other genome projects)?

# Websites for future review as Metabolism class assignments

Nutrition Supplements: Vitamins, Minerals, and Non-Nutrient Supplements