# Metabolomics/Nutrition

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## Introduction to Nutrition and Metabolomics

Metabolomics has been widely adopted in pharmacology and toxicology but is relatively new in human nutrition. The ultimate goal, to understand the effects of exogenous compounds on human metabolic regulation, is similar in all 3 fields. However, the application of metabolomics to nutritional research will be met with unique challenges. Little is known of the extent to which changes in the nutrient content of the human diet elicit changes in metabolic profiles. Moreover, the metabolomic signal from nutrients absorbed from the diet must compete with the myriad of nonnutrient signals that are absorbed, metabolized, and secreted in both urine and saliva. The large-bowel microflora also produces significant metabolic signals that can contribute to and alter the metabolome of biofluids in human nutrition. Notwithstanding these possible confounding effects, every reason exists to be optimistic about the potential of metabolomics for the assessment of various biofluids in nutrition research. This potential lies both in metabolic profiling through the use of pattern-recognition statistics on assigned and unassigned metabolite signals and in the collection of comprehensive data sets of identified metabolites; both objectives have the potential to distinguish between different dietary treatments, which would not have been targeted with conventional techniques. The latter objective sets out a well-recognized challenge to modern biology: the development of libraries of small molecules to aid in metabolite identification. The purpose of the present review was to highlight some early challenges that need to be addressed if metabolomics is to realize its great potential in human nutrition.
American Journal of Clinical Nutrition, Vol. 82, No. 3, 497-503, September 2005 © 2005 American Society for Clinical Nutrition

### What is Metabolomics?

Metabolomics is newly developing field studying the products and effects of the metabolism on the pathological and physiological states within biological samples. Metabolomics offers the possibility of discovering the reasons and causes of certain phenotypes. Another discovery from Metabolomics is the discovery of biomarkers, which reveal changes in health and disease, and can reflect dietary habits. Metabolomics is essential in the study of how specific diets interact with the human body, one of the most important aspects of nutrition.
Koulman, A., and D. A. Volmer. "Perspectives for metabolomics in human nutrition: an overview." Nutrition Bulletin 33.4 (2008)
Small molecule metabolites, the end product of cellular processes, are the most accurate marker of the responses of biological systems resulting from changes either genetic or environmental. There are approximately 2,900 biochemicals (metabolites) that are the key to cellular phenotypes.
Milburn, Michael. "Using Metabolic Profiling Technology to Advance Cell Culture Development." BioPharm International June 2009, p.28-34

### Limitations of Metabolomics

Metabolic profiling has been conducted for over 50 years, which has provided a lot of very helpful information but currently there is not enough data nor a standard way to collect and record data for the study of metabolomics to really be helpful now. Metabolomics has the potential to discover early warning signs of certain diseases as well as determine the effects of certain foods and drugs on the body. This potential could be much greater if more data is collected and recorded accurately and precisely into a database. By recording the effects of age, gender, race, ethnicity, body composition, health, dietary intake, physical activity, stress, and many more factors, people would be able to better interpret their new metabolomic data and advance the general metabolomic knowledge. Without this there is no baseline or control group with which to compare data which greatly hinders proper research and theory creation.
Walsh, M. C. and A. Nugent, L. Brennan and M. J. Gibney. "Understanding the metabolome – challenges for metabolomics." UCD Institute of Food and Health, University College Dublin, Ireland. The British Nutrition Foundation. The Nutrition Bulletin, December 2008. URL: http://web.ebscohost.com/ehost/pdfviewer/pdfviewer?vid=6&hid=109&sid=bd42c8d7-0cb2-4f8b-954e-d93dc1b131df%40sessionmgr111

### Future Of Metabolomics

The future of Metabolomics seems to be coming ever clearer in the wake of increasing scientific innovation in the area of the genome. Through the use and study of various aspects of the genome there has been great scientific improvement which has laid the groundwork for more relevant innovations. Such innovations would include proteome (the study of entire protein complements of cells tissues or fluid compartments), and the metabolome (the study of entire metabolite complements in cells, tissues or fluids) which will support modern nutrition (1). With these scientific leaps in genomic research, Metabolomics, lead by Nutrition, has the potential to reduce disease in both individuals and entire populations. This is all made possible by several innovative and relatively new technologies such as the gene array which performs global gene expression analysis (1). This is just one of the many feats of engineering which have made it possible for us to quantify and understand the human gene and how it relates to Nutrition.
J. B. German, M. A. (2002). Metabolomics and Individual Metabolic Assessment: The Next Great Challenge for Nutrition. The Journal Of Nutrition , URL: http://jn.nutrition.org/cgi/content/full/132/9/2486#BIBL.

## Nutrition, Metabolomics, and Disease

Dysregulation at the level of primary metabolic organs and tissues form the foundation of many diseases. Some primary tissues of current interest include adipose tissue, skeletal muscle, the intestine and liver. The metabolic syndrome, type 2 diabetes and obesity may all be understood as ecological phenomena where metabolism is the primary intermediary between diet and health outcomes. The assessment of essential nutrient status and a comprehensive understanding of metabolic response (e.g. metabolic phenotype) to ecological risk factors is necessary for the identification of effective disease prevention strategies as well as interventions in the clinical treatment of metabolic disease.

### Nutrition and Oral Disease

The below is not medical advice, and is not (as prohibited by government regulation) designed to treat, or prevent any illnesses. The information is currently under review for quality and accuracy.
Nutrition plays a key role in the prevention of many oral diseases, dental caries, dental erosion, developmental defects, oral mucosal diseases and periodontal disease. Poor nutrition can lead to a breakdown in tooth enamel and an increase in oral mucosal. The consumption of soft drinks, which are heavy with acid, has been shown to lead to significant dental erosion. A balanced diet and proper nutrition are essential to the maintaining of a healthy oral system, as well as the rest of the body. Bacteria can also cause periodontal disease, gum disease, and erosion. Chewing antibiotics is one way to prevent periodontal disease.
Periodontal disease, an oral infectious disease involving inflammation and loss of bone and supporting tissues, progresses more rapidly in undernourished developing populations around the world. Many local and systematic factors influence the severity and longevity of progression of the common yet preventable disease.
Malnutrition however exacerbates the severity of oral infections, which are contributing factors to other life-threatening diseases. Deficiencies in vitamin C lead to scurvy, while deficiencies in vitamin A, D and other protein-energy components are associated with enamel hyplosia and salivary gland atrophy. Antioxidant intake in foods, such as pomegranate seeds, green or black teas, have been used as buffers of reactive oxygen species that lead to tooth decay. Antioxidants are found in high fruit and vegetable diets and have been determined to contain anti carcinogenic properties. Diet plays an important role in the dynamic equilibrium of dimineralization-remineralization of the tooth surface. Therefore, food's form, frequency of sugar and alcohol intake, and combination of vital nutrients and minerals play an important role in maintaining a healthy oral system.
Moynihan, Paula J. "The role of diet and nutrition in the etiology and prevention of oral diseases." Bulletin of the World Health Organization 83.9 (2005)
Position of the American Dietetic Association: Liberalization of the Diet Prescription Improves Quality of Life for Older Adults in Long-Term Care Journal of the American Dietetic Association - December 2005 (Vol. 105, Issue 12, Pages 1955-1965, DOI: 10.1016/j.jada.2005.10.004)
Rugg-gunn A. Nutrition, diet and oral health. Journal of the Royal College of Surgeons of Edinburgh [serial online]. December 2001;46(6):320. Available from: Academic Search Complete, Ipswich, MA. Accessed June 3, 2010.

### Nutrition and Celiac disease

Celiac disease (CD) is an inflammatory small intestinal disorder that can lead to severe villous atrophy, malabsorption, and malignancy. It is triggered by the gluten proteins of wheat, barley, and rye. All patients express the antigen presenting molecules human leukocyte antigen-DQ2 (HLA-DQ2) and/or HLA-DQ8, which bind gluten peptides and thus activate destructive intestinal T cells. Patients with untreated CD have circulating IgA autoantibodies to the enzyme tissue transglutaminase (tTG), a component of endomysium. Testing for serum IgA tTG has a high predictive value. Therapy of CD is a lifelong gluten-free diet. Counseling by an expert dietitian and association with a celiac support group are important in helping the patient embark on a healthy gluten-free diet. Current research focuses on non-dietary therapies and treatment of refractory (diet-unresponsive) CD.
Kelly, Ciaran P., Dennis, Melinda D., Schuppan, Detlef. “Celiac Disease: Epidemiology, Pathogenesis, Diagnosis, and Nutritional Management”. Nutrition in Clinical Care (April 2005).
There is an estimated prevalence of 1% in North America. Typically symptoms become present in early childhood and consist of abdominal cramps, diarrhea, malabsorption and nutrient deficiencies. A link has been found with giving infant cereal, which contains gluten, too young and developing Celiac disease. Parents are advised to wait until 4-6 months of age before giving babies infant cereal. In a study of over 1500 children 51 developed the disease and those who were exposed to infant cereal before 3 months were at 5 times more likely to develop the disease.
Belanger, Jeanette E.; Wooltorton, Eric; "Is the timing of infant cereal introduction a risk factor for celiac disease autoimmunity?" Canadian Medical Association Journal p.1374, November 22, 2005

### Nutrition and Childhood Obesity

The rapid increase in the prevalence of obesity in children and adolescents is alarming, particularly in light of its many medical and psychosocial consequences.Due to the multifactorial etiology of overweight and obesity, action is needed concurrently at many levels. Physicians should screen for overweight and obesity regularly in order to address the problem at an early stage. One promising approach is to introduce healthy eating habits, focusing on portion control and a diet rich innon-starchy vegetables, fruits, and legumes, and sufficient in moderate-glycemic index/load foods, protein, healthy types of fat, and reduced-fat dairy foods. In addition, it is important to decrease sedentary behaviors and increase physical activity. The earlier a healthy lifestyle is introduced into a child's life, the more likely it is to become a way of life. Parents have a major role to play in controlling what their young child eats and in reinforcing healthy eating at an early age, serving as role models themselves. Interventions that include the whole family in the process are likely to have the most success in the prevention and treatment of childhood overweight and obesity.
Philippas, Niki G, Lo, Clifford W. “Childhood Obesity: Etiology, Prevention, and Treatment”. Nutrition in Clinical Care. (April 2005).

### Nutrition and the link between Childhood Obesity and Severe Adult Obesity

Childhood obesity not only affects the health and nutrition of a child’s life, but also puts them at a higher risk of having severe adult obesity. In a study done by Ilonna and Alfred Rimm where they conducted a questionnaire completed by 73,532 women, they found that a large portion of severely obese women were also obese children. The data found from their study also suggests that the risk of an overweight child developing severe adult obesity is significantly greater than that of non-obese children. Since adult obesity can be linked to so many health problems and adult diseases, this study shows the importance of weight control through childhood.
Rimm, Ilonna J., and Alfred A. Rimm, PHD. "Association between Juvenile Onset Obesity and Severe Adult Obesity in 73,532 Women." Public Health Briefs66.5 (1976): 479-81. Print.

## Obesity and the Link to Malignant Cancer

Not only does being obese contribute to things like cardiovascular disease and diabetes, research has shown that it can also be linked to an increased risk of cancer. Researchers estimate that excess weight may account for 14 percent of cancer death in men and 20 percent of cancer deaths in women. As far as preventable risk factors for cancer go, only smoking rates higher. There is a major connection between cancer and insulin, which happens to be one of the main hormones that responds to obesity. The more obese the individual, then typically the more insulin they will have in their system. Also, concentrations of hormones that cause inflammation may rise with fat concentrations, which also may set cancer in motion Any of these fluctuations in hormone levels could work together to initiate carcinogenesis.
Nutrition Health Review: The Consumer's Medical Journal; 2009, Issue 100, p8-8, 1/2p

## Maternal Influence on Nutrition

Adequate nutrition and balance of vitamins has a huge effect on human growth before we are even born. During pregnancy, it is important for mother’s to maintain proper balances of vitamins and minerals in order to support the long term develop and health of the metabolism in her child. A recent study published in The New England Journal of Medicine indicated the importance of Vitamin A, for example. The article notes that “vitamin A deficiency in a mother during pregnancy could have lasting adverse effects on the lung health of her offspring” by not providing the child with the support it is needs to build healthy alveoli of the lungs (West et. Al 2010). Properly developed lungs, help contribute to the overall health of an infant. Other research has also determined the importance of micronutrients in a mother’s diet that help support a healthy baby. Mother’s who maintained diets high in micronutrients and vitamins found in green leafy vegetables, fruit and milk tended to have larger and healthier babies. The study also notes that mother’s who had high levels of glucose; insulin, cholesterol, and triglycerides during pregnancy increased the chances that their child would develop higher insulin resistance, which is one of the main causes of diabetes (Yajnik 2006).
Checklye W, West KP Jr, Wise RA, Baldwin MR, Wu L, LeClerg SC, Christian P, Katz J, Tielsch JM, Khatry S, Sommer A. 2010. Mineral Vitamin A Supplementation and Lung Function in Offspring. New England Journal of Medicine. 13:362(19): 1784-94.
Yajnik, Chittarani. 2006. Nutritional Control of Fetal Growth. Nutrition Reviews. 64(5): 49-51.

### Iodine Deficiency in Pregnancy

Iodine is necessary for the synthesis of the thyroid hormones. Nearly 80 percent of the iodine in the body is found in the thyroid gland, most of it is the thyroid hormones. The amount of iodide, a form of iodine, in drinking water generally depends on the iodine content of local soil. Some 10 percent of the world population is at risk of developing iodine deficiency because they live at high altitudes where the drinking water is low in iodide. To counteract low iodine levels iodide is sometimes added to commercial table salt.
In iodine deficiency, the thyroid gland attempts to capture more iodide for the synthesis of thyroid hormones and enlarges. The iodide level in the blood and urine is very low. A pregnant woman who is deficient in iodine may have a baby whose brain is improperly developed because of iodine deficiency. This condition is called cretinism (Beers: 1999). Cretinism is marked by irreversible mental and growth retardation (Tatsumi: 1992).
The Merck Manual, 17th ed. Mark H. Beers, MD, Robert Berkow, MD, eds. Whitehouse Station, NJ: Merck Research Labs, 1999.
Ke-ita Tatsumi1, Kiyoshi Miyai1, Tsugunori Notomi1, Kyoko Kaibe1, Nobuyuki Amino1, Yuji Mizuno2 & Hitoshi Kohno.3 “Cretinism with combined hormone deficiency caused by a mutation In the PIT1 gene” Nature Genetics 1, 56–58 (1992) doi: 10.1038/ng0492-56

## Nutrient specific sections

The are many types of vitamins classified by the materials in which they will dissolve, two of which are: Fat Soluble and Water Soluble. Others are Calcium, Fish Oil, Flax Seed, Iron, Vitamin K, Vitamin E, and Vitamin D.

### Calcium

Calcium is mineral that is the most likely to be deficient in the human diet. 99% of the calcium in the human body is stored in the bones and teeth. It is the most supportive element in bones and teeth and makes up 70% of bone weight and accounts for bone strength. The last 1% floats in the bloodstream and performs a variety of functions throughout the body. It also helps in contracting muscles and regulating the contractions of the heart. It also plays a key role in the transmission of nerve impulses and in blood clotting. It is also involved in the stimulation of contractions during childbirth as well as milk production. In order for the body to absorb calcium, there needs to be Vitamin D in the blood. Vitamin D is a key ingredient that enables calcium to pass from the digestive system into the bones or blood. Even though everyone knows that calcium is important in a healthy adult diet, some people still don’t get enough and end up being deficient. Calcium deficiency causes the bones to weaken and thin out and can even cause them to be brittle. It also causes osteoporosis which means that the bones have developed tiny holes and increases risk of fracture. Osteoporosis seems to affect women more often than men. So, for the average adult, ingest 1000mg of calcium and you will continue to grow up big and strong.
References: http://www.thedietchannel.com/What-You-Should-Know-About-Calcium-Deficiency.htm; http://www.vitamins-nutrition.org/vitamins/calcium.html
At the other end of the spectrum, a study was done by Taru K Pilvi et al. to investigate energy restriction and its effect on weight loss. As a further investigation, this study also aimed to explain "whether the [weight-loss] effect of energy restriction can be further enhanced by modification of dietary protein source and calcium." They found that the increased levels of dairy protein and calcium had a "significant effect on hepatic lipid changes." The mice of this study that were fed a diet with increased levels of whey protein and calcium exhibited a reduction in "the relative level of potentially diabetogenic ceramides and diacylglycerols to the level observed in lean animals." Another study showed similar effects of increased dairy in the diet of obese subjects. This study done by Zemel MB et al. showed a direct association between increased dietary calcium and lipid utilization. Both of these studies concluded that increased calcium consumption during energy restriction results in augmented weight loss in obese individuals.
References: Taru K Pilvi et al. 2008. Metabolomic changes in fatty liver can be modified by dietary protein and calcium during energy restriction, World J Gastroenterol, 14(28): 4462–4472. Zemel MB et al. 2005. Dairy augmentation of total and central fat loss in obese subjects, International journal of obesity, 29(4):391-397.

### Fat Soluble Vitamins

Fat soluble vitamins can be very important to some people more than others for many reasons. The American Society for Nutrition claims that, "fat-soluble vitamins are needed for maintaining optimal function of innate and adaptive immune cells." In that case, fat soluble vitamins can help improve immune response to tumors. However, that is not the only thing that fat soluble vitamins can help improve. There are a variety of fat soluble vitamins that can improve health. The beneficial effects can vary considering that they can improve different aspects of the human body. Fat-soluble vitamins -- vitamins A, D, E and K -- dissolve in fat before they are absorbed in the blood stream to carry out their functions. Excesses of these vitamins are stored in the liver. Because they are stored, they are not needed every day in the diet.
Meydani, Simin (2005), Are Fat-Soluble Vitamins Effective in Enhancing Tumoricidal Cell Activity?, The Journal of Nutrition
* Vitamin A
* Vitamin K

### Fish Oil

Fish oil is found in omega 3 and is part of long-chain polyunsaturated fatty acids. It a natural oil usually produced from the body of cold-water fish. The generic name is vitamin A and the brand names are A-25, A/Fish Oil, Aquasol A which comes in a capsule form with soft gel liquid inside. It is known as the marine oils and is essential fatty acids that are found in fish. There are two main ingredients to fish oil. One is the 20 carbon eicosapentaenoic acid (EPA). The other is the 22-carbon docosahexaenoic acid (DHA). The average fish oil supplement is 20 EPA and 10 DHA for a total of 30 omega-3, which may help to keep block triglycerides in check and help protect against atherosclerosis. Studies have found that fish oil may help prevent Crohn's disease, high blood pressure, high triglycerides and rheumatoid arthritis. Fish oil is also good for the brain because the brain is one of the largest consumers of DHA. It can be known as brain food.
Reference: http://www.nutrasanus.com/fish-oil.html, http://vvv.com/healthnews/fishoils.html
In one Australian study, fish oil supplements taken by women during pregnancy were associated with improved hand-eye coordination of their children. It is also suggested that high doses of fish oil are beneficial in the last weeks of pregnancy and further research is being done to determine the ways in which it is.
Reference: http://www.nytimes.com/2007/01/02/health/nutrition/02nutr.html?scp=3&sq=fish+oil+supplements&st=nyt
Populations that consume large amounts of fish have been associated with reduced incidences of breast cancer. LIke it has been said, fish oil is high in omega-3 fatty acids (EPA and DHA), and research is being done to determine whether it is that aspect of fish that seems to contribute to protection against breast cancer.
Reference: http://escholarship.org/uc/item/12g6398b?query=fish%20oil

### Flax Seed

According to health experts, the seed of the blue-flowering flax plant that can be easily found on Canadian and Mesopotamian soil, is packed with disease-fighting nutrients and fiber. It is also loaded with two fatty acids that are necessary for our bodies: omega-3s and lingans, which also work as natural antioxidants. The omega-3s in the flax seed help remove toxins from the human body, as well as helping with the prevention of heart disease and inflammation. The lignans aid with the prevention of cancers and provides 700 times the amount of fiber that can be found in legumes or whole grains. This fiber is also great for fighting bad cholesterol and type 2 diabetes. Omega-3 and lignan are essential to every membrane and cell in the human body, making them extremely beneficial. Flax seed has the ability to fix radical oxygen atoms. Radical oxygen molecules can cause molecular damage to DNA, shortening and damaging it. They are associated with the deterioration of the body often associated with aging.
Flax seed also has notable effects on the menstrual cycle. It prolonges the fertile stage of the menstrual cycle, the luteal phase. It also helps regulate the release of an ovum. Women that regularly consume flax seed are more likely to release an egg for every menstrual cycle they have than women who have a low fiber diet withno flax seed supplements. Two phytochemicals in flax seed are linked to changes in the female hormonal cycle associated with these changes in the menstrual cycle. They are absorbed in the intestines and affect the ratios of estrogen, progesterone, and testosterone during different times in the menstrual cycle. A study at Duke University found that men scheduled for prostate cancer surgery who began eating two teaspoons of flaxseed oil daily, showed that within 30 days the flax seed halted tumor growth and many of the cancer cells had self-destructed. Although all parts of the flax seed including the seed, oil, or both would benefit our diets, shopping for flaxseed can prove difficult as there are so many processed variations of the plant, each of which with its own care instructions. Be sure to read the back of all packaging’s to make sure you choose the best one for you.
Reference: Rubin, Tina. "The Flax of Life." Better Nutrition Apr. 2010: 54. Print.
Prasad, Kailash. "Hydroxyl radical-scavenging property of secoisolariciresinol diglucoside (SDG) isolated from flax-seed ." Molecular and Cellular Biochemistry Mar. 1997: 168. Print.
WR Phipps, MC Martini. "Effect of flax seed ingestion on the menstrual cycle." Journal of Clinical Endocrinology & Metabolism 1993: 77. Print.

### Iron

Iron is split into two categories. HEME iron can be obtained only from meat, fish and poultry and is an easier type of iron for the body to break down and use as a nutrient. NON-HEME iron can be obtained from fruits, vegetables, beans, nuts and grains and is more difficult for the body to absorb. The Recommended Dietary Allowance (RDA) for males aged 19 to 50 is 8mg/day. Females in the same age range are suggested to consume 18mg of iron per day. Iron deficiency is the number one nutritional disorder in the world. It can be caused by a low dietary intake of iron or the inability to absorb the iron consumed. Also, excessive blood loss is another factor. Women are at a higher risk for iron deficiency because of the consistent menstrual blood loss experienced during their menstrual cycle. To help fight iron deficiency many breakfast cereals are iron-fortified shown on the nutrition label.
Reference: http://ods.od.nih.gov/factsheets/iron.asp#h4 http://www.mckinley.illinois.edu/Handouts/dietary_sources_iron.html
Iron is both an essential nutrient and a potential toxicant to cells, requiring a highly sophisticated and complex set of regulatory approaches to meet the demands of cells as well as to prevent excess accumulation. For humans, iron plays a central role in oxygen transport and the synthesis of haemoglobin, myoglobin, and some important enzymes to energy production. Many studies have demonstrated that iron deficiency may impair the performance of athletes, so normal iron status in athletes is especially important. Exercise alone may not lead to a true iron deficiency, but probably results from dietary choices, inadequate iron intake, and menstruation. Iron deficiency affects particularly pregnant women, young children, and adolescents. Iron is a micro-nutrient and is required for regulation of brain neurotransmitters by altering the pathway enzymatic system. Studies have shown that iron deficiency in infants can negatively impact neurological development necessary later in life. It is thought that early iron deficiency can possibly impair the development and function of the hippocampus in the brain, which plays an important role in developing and retaining long-term memories. Iron deficiency in infants might also impair the dopamine system. It is possible that those adolescents who were exposed to chronic and sever iron deficiency in their infant stages may exhibit deficits on tests in things like Spatial Working Memory, Rapid VIsual Information Processing, Pattern Recognition Memory, and Spatial Recognition Memory.
Reference: Qian, Zhong Ming. "Nitric Oxide and Changes of Iron Metabolism in Exercise". Cambridge Journals.
Agarwal, Kailash N. "Iron and the Brain: Neurotransmitter receptors and Magnetic Resonance Spectroscopy". British Journal of Nutrition.
Lukowski, Angela F. "Iron deficiency in infancy and neurocognitive functioning at 19 years: evidence of long-term deficits in executive function and recognition memory."

#### Vitamin K and Vitamin E Interactions

As noted above each vitamin is necessary "for maintaining optimal function of innate and adaptive immune cells" yet it is important to remember that each vitamin also interacts with the others. Interestingly, some studies have indicated that Vitamin E may decrease Vitamin K's addition to the immune system. Though the connection has not been proven, preliminary clinical trials have reflected that Vitamin K's metabolism is slowed with an excess of Vitamin E. One hypothesis is that Vitamin K and E compete for the enzyme. So far only rats have been tested, though it has been observed with statistical significance that when an excess of Vitamin E is present there are far fewer MK-4's (the metabolized Vitamin K).
Vitamin A is a vitamin that is needed by the retina of the eye in the form of a specific metabolite, the light-absorbing molecule retinal. This molecule is necessary for both scotopic and color vision. Vitamin A also functions in a very different role, as an irreversibly oxidized form of retinoic acid, which is an important hormone-like growth factor for epithelial and other cells. Vitamin A can be found in two principal forms in foods: Retinol which is the form of vitamin A absorbed when eating animal food sources. The carotenes alpha-carotene, beta-carotene, gamma-carotene; and the xanthophyll beta-cryptoxanthin (all ofwhich contain beta-ionone rings), function as vitamin A in herbivores and omnivore animals. The discovery of vitamin A may have stemmed from research dating back to 1906, indicating that factors other than carbohydrates, proteins, and fats were necessary to keep cattle healthy. Adequate supply of Vitamin A is especially important for pregnant and breastfeeding women, since deficiencies cannot be compensated by postnatal supplementation. However, excess Vitamin A, especially through vitamin supplementation, can cause birth defects and should not exceed recommended daily values. Since vitamin A is fat-soluble, disposing of any excesses taken in through diet is much harder than with water-soluble vitamins B and C, thus vitamin A toxicity may result. This can lead to nausea, jaundice, irritability, anorexia vomiting, blurry vision, headaches, hairloss, muscle and abdominal pain and weakness, drowsiness, and altered mental status. Toxic effects of vitamin A have been shown to significantly affect developing fetuses. Therapeutic doses used for acne treatment have been shown to disrupt cephalic neural cell activity. The fetus is particularly sensitive to vitamin A toxicity during the period of organogenesis.
Reference: Traber, Maret G. (2008). "Vitamin K Interactions a 50-year Problem." Nutrition Reviews, 66(11):624-629, doi: 10.1111/j.1753-4887.2008.00123.x.

## Vitamin D

Vitamin D is sometimes known as the “sun-shine vitamin” due to it's ability to fight off infections. It is also important for bone health. It can protect against osteoporosis, arthritis and other bone problems. In the study of Osteoporotic fractures in men study, researchers found that low vitamin D levels were connected to a greater possibility for arthritis, whereas men with higher vitamin D levels had reduced chances of developing arthritis. With a sufficient intake of Vitamin D, it is possible to build a defense against arthritis, as the vitamin D helps to regulate the development and maintenance of bone and cartilage.
Vitamin D has been recently found to have many additional health benefits outside of bone health. People with sufficient vitamin D levels have been found to have increased testosterone and muscle mass. Gaining your vitamin D solely through sunshine is generally not enough to maintain a healthy level.
Vitamin D supplements are widely recommended for people who live in environments that don’t receive an adequate amount of sunshine. Vitamin D is one of the body’s essential vitamins and a 2010 study by Japanese researchers suggest there might be a link between vitamin D and flu prevention. Although more studies will be necessary to make a conclusive link, there was an 8% decrease in flu diagnoses among children who received the recommended 700-1000 IU a day as compared to those receiving a placebo.
Vitamin D is one of many important body essential vitamins that help balance the body. It is known to be an immune system regulator. Researchers states that, “the active form of vitamin D, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], has been shown to inhibit the development of autoimmune diseases, including inflammatory bowel disease (IBD).” In total reverse of proper Vitamin D intake and low counts of Vitamin D receptors, it can result in accelerated inflammatory bowel disease. Dietary calcium can help trigger the effects of Vitamin D on the immune system because it has its own independent effects on inflammatory bowel disease. Therefore 1,25(OH)2D3 treatment of mice on low-calcium diets can improve the symptoms of inflammatory bowel disease.
Vitamin D is a group of fat-soluble secosteroids, the two major physiologically relevant forms of which are vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol). Vitamin D without a subscript refers to either D2 or D3 or both. Vitamin D is produced in the skin of vertebrates after exposure to ultraviolet B light, and occurs naturally in a small range of foods. In some countries staples such as milk, flour and margarine are artificially fortified with vitamin D, and it is also available as a supplement in pill form. Vitamin D is carried in the bloodstream to the liver, where it is converted into the prohormone calcidiol. Circulating calcidiol may then be converted into calcitriol, the biologically active form of vitamin D, either in the kidneys or by monocyte-macrophages in the immune system. When synthesized by monocyte-macrophages, calcitriol acts locally as a cytokine, defending the body against microbial invaders. When synthesized in the kidneys, calcitriol circulates as a hormone, regulating, among other things, the concentration of calcium and phosphate in the bloodstream, promoting the healthy mineralization, growth and remodeling of bone, and the prevention of hypocalcemic tetany. Vitamin D insufficiency can result in thin, brittle, or misshapen bones, while sufficiency prevents rickets in children and osteomalacia in adults, and, together with calcium, helps to protect older adults from osteoporosis. Vitamin D also modulates neuromuscular function, reduces inflammation, and influences the action of many genes that regulate the proliferation, differentiation and apoptosis of cells. Important that Washington citizens try to find time to get out in the sun and get there vitamin D. there are a vast array of consequences for the human body that does no obtain enough vitamin D. So get out there and get your sunshine.
Cantorna, M.T, Zhu, Yan, Froicu, Monica and Wittke, Anja (2004), Vitamin D status, 1,25-dihydroxyvitamin D3, and the immune system, The American Journal of Clinical Nutrition
There was a study done about the correlation between milk consumption and prostate cancer. The study, although far from having definite answers seemed to find a pattern in the decreased rates of prostate cancer in men who take in lots of vitamin D. The vitamin D seems to have some sort of preventative effect on prostate cancer. It was certainly found that men who take in less vitamin D have a greater chance of getting and dying from prostate cancer. The study did find that the calcium in milk decreases the production of vitamin D3 which in turn cancels out the beneficial effects of the vitamin. In other words vitamin D from milk, although still good for you, does not have to preventative effect on prostate cancer as a healthy does of pure vitamin D does. Givens, D. I. and R. Morgan and P. C. Elwood. "Relationship between milk consumption and prostate cancer: a short review." Animal Science Research Group, School of Agriculture, Policy and Development, Faculty of Life Sciences, University of Reading, Reading, UK; Department of Primary Care and Public Health Centre for Health Sciences Research, Cardiff University, Neuadd Meirionnydd, Heath Park, Cardiff, UK. December 2008 http://web.ebscohost.com/ehost/pdfviewer/pdfviewer?vid=6&hid=109&sid=c363fced-4af5-4cc1-8834-e7cbab5d40a6%40sessionmgr113
Brown, Jordana, Doing the D, Joe Weider's Muscle and Fitness, 2010 Weir, Kirsten, D Plus, Current Science, 2010 Can D Fight Off the Flu?, Nutrition Action Health Letter, 2010
Vitamin D Signals Immune System to Fight Infections, Tufts University Health & Nutrition Letter, 2010
* Vitamin E

### Water Soluble Vitamins

B-complex vitamins and vitamin C are water-soluble vitamins that are not stored in the body and must be replaced each day.These vitamins are easily destroyed or washed out during food storage and preparation.The B-complex group is found in a variety of foods: cereal grains, meat, poultry, eggs, fish, milk, legumes and fresh vegetables. Citrus fruits are good sources of vitamin C. The use of megadoses of vitamins is not recommended and in some cases can have undesirable results. In 2010, Canadian researches studied 238 people with chronic kidney disease, challenging earlier studies that had suggested B vitamins could protect the kidneys because they lower blood levels of homocysteine, an amino acid that is linked to a higher risk of kidney damage. Yet after three years of studies it was found that those who got the high-dose B vitamins had a greater decrease in kidney function that those who received the placebo. Vitamins are essential nutrients found in foods. The requirements are small but they perform specific and vital functions essential for maintaining health. Water-soluble vitamins dissolve in water and are not stored; they are eliminated in urine. We need a continuous supply of them in our diets. The water-soluble vitamins are the B-complex group and vitamin C.
Water-soluble vitamins are easily destroyed or washed out during food storage or preparation. Proper storage and preparation of food can minimize vitamin loss. To reduce vitamin loss, refrigerate fresh produce, keep milk and grains away from strong light, and use the cooking water from vegetables to prepare soups N, J (Jun 2010), B Vitamins Harm Kidneys, Nutrition Action Health Letter
Anderson, J (2008), Water Soluble Vitamins, Colorado State University
* Vitamin C
* Folate
* Dietary fiber