Basics of Vitamin A

Vitamin A: Functions, Forms, Food sources, Deficiency and Toxicity

What are the functions of vitamin A?

Stanfield and Hui (2011), define vitamins as a group of essential organic compounds required daily in very small amounts (mostly milligrams) for the normal functioning of the body. According to Ball (2008), Vitamins have unique varying functions in the body including the regulation of gene expression (Vitamins A and D, thiamin, vitamin B12), structural roles in visual pigments (vitamin A as retinal), function as anti-oxidants (vitamins A, E, and C) and, as enzyme cofactors (the B group vitamins and Vitamin K (Dryden, 2008). 

Vitamin A along with other fat soluble vitamins is found in foodstuffs in association with lipids and is absorbed along with dietary fats by mechanisms similar to fat absorption (McDowell, 2008).

According to Seth (2011), the various functional forms of vitamin A have  correspondingly different functions in the body. Retinol aids in transport and reproduction (Dente and Hopkins, 2010),  retinyl esters are important in storage, retinal plays a key role in vision whereas the function of retinoic acid is demonstrated in epithelial differentiation, growth and transformation. The most widely recognized role played by vitamin A is its function in vision (Combs, 2012). Retinol is utilized in the aldehyde form (trans-form to 11-cis-retinal) in the retina of the eye as the prosthetic group in rhodopsin for adaptation to darkness i.e. rods (Berdainer, 2010) and as the prosthetic group in iodopsin for bright light and color vision i.e. cones (McDowell, 2008). In maintenance of integrity of the cornea, retinoic acid is needed to sustain appropriate cell differentiation (Herrmann and Obeid, 2011).

Vitamin A has gained a reputation as an anti-infective vitamin (Whitney et al., 2011) essential for normal immune system maturation and function. There is evidence to suggest that vitamin A deficiency is a risk factor for low antibody production (Hulea, 2008) and,  that vitamin A plays a role in maintenance of integrity of  epithelial surfaces and development of  the lymphoid system (Shetty, 2010). Vitamin A stimulates antitumor activity in cancer cell lines. All-trans-retinoic acid exhibited an inhibitory effect on cell growth, cell cycle and alkaline phosphatase activity in human pancreatic cancer cells in vitro (Guo et al., 2006).

Vitamin A especially as retinoic acid is required for differentiation of epithelial cells. Cell differentiation is a process by which immature cells are transformed into specific type of mature cells, which form protective linings on many of the body’s organs (Gropper et al., 2009).  The integrity of the respiratory, gastrointestinal, and urogenital tracts, as well as the eye, are protected from environmental influences by mucous membranes (Elias and Ketcham 2007). Retinoids perform the latter function in a way that steroid hormones do; this is by binding to the nuclear chromatin to signal transcriptional processes. Further retinoic acid has been found to stimulate, synergistically with thyroid hormone, the production of growth hormone in cultured pituitary cells (Combs, 2012).

Vitamin A functions as an antioxidant to reduce markers of oxidative damage and inflammation, and therefore may be helpful in preventing initiation and progression of diseases due to oxidative stress (Prasad, 2008). Beta carotene is one of the many dietary anti-oxidants present in foods- others include, vitamin E, Vitamin C, the mineral selenium and various phytochemicals (Whitney et al., 2011). A study from 1989 to 1995 showed that higher serum levels of beta- carotene, total carotene, provitamin A and total carotenoid reduced the harzadous ratios for mortality rates of patients with cardiovascular diseases and cancer at all sites. (Ito et al., 2006).Vitamin A itself is physiologically significant in this regard, as retinol and retinal cannot quench singlet oxygen and have only weak capacities to scavenge free radicals. It however can affect tissue levels of other antioxidants. Several carotenoids, on the other hand, have been shown to have direct antioxidant activities. These include beta-carotene, lycopene and some oxycarotenoids (like lutein and zeaxanthin), which can quench singlet oxygen or free radicals in the lipid membranes into which they partition (Combs, 2012).

Forms and Sources of Vitamin A

Vitamin A is generally classified into two main groups possessing biological activity: (i) C-20 unsaturated hydrocarbons including retinol and its derivatives from animal origin (b) C-40 unsaturated hydrocarbons including carotene and a number of other provitamin A carotenoids of plant origin (Heldman and Lund, 2006).

Preformed vitamin A is found in foods of animal origin the richest sources being liver and fish oil. Milk and milk products and vitamin A fortified foods such as enriched cereals can also be good sources. Even butter and eggs provide some vitamin A (Sizer and Whitney, 2013).  Eating liver once a week or so is enough to provides the recommended daily intake. Butter and eggs also provide some vitamin A to the diet. Because vitamin A is fat soluble, it is lost when milk is skimmed. To compensate, reduced-fat, low-fat and fat-free milk are often fortified with vitamin A. Margerine is also usually fortified so as to provide the same amount of vitamin A as butter (Whitney et al., 2011).

Retinoids refer to any natural or synthetic form of vitamin A ( Messonnier, 2010). Retinol is the alcohol form of vitamin A. Replacement of the alcohol group by an aldehyde group gives retinal, and replacement by an acid group gives retinoic acid. Esters of retinol are called retinyl esters. Vitamin A in animal products exists in several forms, but the principally exists as long chain fatty acid esters (McDowell, 2008). In several varieties of seawater and freshwater fish, vitamin A2 is present as a major form of vitamin A. Vitamin A2 differs from vitamin A in chemical structure as it has an addition double bond in the cyclohexene ring at the 3,4 position ( Herrmann and obeid, 2011). The most active form of vitamin A is the all-trans vitamin A. the cis-forms may arise from the all trans-form, and there is a loss of vitamin A potency due to the conversion. These changes are promoted by moisture, heat, light and catalysts (McDowell, 2008).

Carotenoids are usually found in plants and plant products as in inactive forms. They are referred to as provitamin A or vitamin precursors because the body can convert them into active vitamin A (Insel et al., 2012). The carotenoids are a diverse group of more than 600 naturally occurring pigments. All of the carotenoids are antioxidants, and approximately 50 are considered vitamins because they have pro-vitamin A activity (Morley and Thomas, 2007). Four of these including α-carotene, β-carotene, γ-carotene, and cryptoxanthine have vitamin A activity of which β-carotene has the greatest activity. Theoretically, I mol of β-carotene could be converted to 2 mol of retinal whereas 1 mole of other provitamin A carotenoids yield only one mol of retinal (McDowell, 2008). Carotenoids can further be classified into provitamin A and non-provitamin A carotenoids. Provitamin A carotenoids include beta –carotene, alpha-carotene, gamma-carotene, beta-cryptoxanthin and alpha-cryptoxanthin (Victor, 2012). Provitamin A carotenoid absorption is usually low, at around 10-20% and not all absorbed provitamin A carotenoids are cleaved into vitamin A activitive compounds (Bohn, 2008). Non-provitamin A carotenoids include lutein, lycopene, zeaxanthin and astaxanthin and according to Sayo et al., (2013) the molecular basis of their biological activities is not fully known.

Many plant foods contain beta-carotene, the orange pigment responsible for the bold colors of many fruits and vegetables. Carrots, sweet potatoes, pumpkins, cantaloupe, and apricots are all rich sources and their bright orange color enhances the eye appeal of the plate. Dark green vegetables, such as spinach, other greens, and broccoli, owe their color to both chlorophyll and beta-carotene. However colorful vegetables like iceberg, lettuce, beets and sweet corn don’t contain beet carotene as it my perceived (Whitney et al., 2011). The vitamin A activity of fruits is generally lower than that of leafy vegetable. However fruits have more acceptance than vegetables especially in children.  Mango, papaya and watermelon have the highest concentration of provitamin A carotenoids (Sommerburg et al., 2013). The carotenoid content of foods is highly variable and is affected by a number of factors including genotype (variety and cultivar), season, geography, cultivation variation, stage of maturity at harvest, handling and postharvest storage conditions (Tanumihardjo, 2012).

Vitamin A and Night Vision

Vitamin A allows for night and color vision as is a functioning part of the retina. The retina contains both rod and cone cells. The former are of interest in low light vision and are rich in a purple pigment rhodopsin also known as visual purple (Insel et al., 2012). Retinol is utilized in the aldehyde form in the retina of the eye as the prosthetic group in rhodopsin for dim light vision (rods) (McDowell, 2008). Each rhodopsin molecule is composed of a protein called opsin bonded to a molecule of the retinal form of vitamin A (Whitney et al., 2011).

When light strikes rhodopsin, cis-retinal changes in configuration to trans-retinal, subsequently separating from opsin. This metabolic conversion, in turn, causes a series of reactions leading to a decrease in sodium entry to sodium channels and a change in membrane potential that is transmitted to the brain. This neural signal is seen as light and is transformed into an image that you recognize (Desai, 2000). A visual cycle is completed when trans-retinal is converted back to cis- retinal which in turn combines with opsin in the outer segment to form rhodopsin. (Gibney  et al., 2012). However, trans-retinal is not recycled to cis-retinal with 100% efficiency. Instead, some trans-retinal is converted to retinoic acid, which cannot be used to form rhodopsin. Extra retinal must therefore always be available for vision to remain optimal. Without enough retinal to reform, night vision becomes especially difficult, resulting in a condition called night blindness (Mcguire and Beerman, 2011).The role played by vitamin A in night vision (dark adaptation) is illustrated in figure 1.

Vitamin A Deficiency

McDowell (2008), states that vitamin A is one of the few vitamins whose deficiency or excessive amounts constitute a health hazard. Vitamin A deficiency affects over 250 million preschool children of which close to 500,000 become blind every year and half of them die within 12 months of losing their sight (WHO, 2013). The deficiency is more prevalent in the developing world due to inadequate intake whereas toxicity is commonly found in the developed world as a result of supplementation. Up to a year’s supply of vitamin A can be stored in the body, 90 percent of it in the liver (Whitney et al., 2013).  The extent of vitamin A deficiency can be assessed by biochemical measures such as plasma or serum retinol or retinol-binding concetrations (Semba and Bloem, 2008).

According to McDowell (2008), a diet deficient in Vitamin A causes lesions in the eye, the process of keratinization leads to drying and hardening of the cornea, which may progress to permanent blindness. Vitamin A deficiency is the major cause of preventable blindness in children (Whitney eta al, 2013),  loss of vision due to a failure of rhodopsin formation in the retina; defects in bone growth; defects in reproduction (e.g., failure of spermatogenesis in the male and resorption of the fetus in the female); and defects in growth and differentiation of epithelial tissues frequently resulting in keratinization of tissues including; the alimentary ,the genital, reproductive, respiratory and urinary tracts (McDowell, 2008).To prevent the severe deficiencies of vitamin A, the RDI is recommending 5,000 international units for men and women, and 8,000 international units for pregnant and lactating women (Bruning and Lieberman, 2007).

Vitamin A Toxicity

For optimum general health, the basic optimum daily intakes for Vitamin A are 5,000-25,000 IU for men and women respectively and for beta-carotene are 11,000-25,000IU for men and women respectively (Lieberman et al., 2007). Unlike the water soluble vitamins B and C that are easily eliminated from the body, vitamin A is fat soluble and therefore hard for the body to eliminate it (Asprey and Asprey, 2012). The hepatic storage of vitamin A tends to mitigate against the development of intoxication due to intakes in excess of physiological needs (combs, 2012). Both forms of active vitamin A i.e. both fat and water soluble are stored in the liver and can hence be toxic in excess amounts. However, toxicity is commonly due to persistent large overdoses of preformed vitamin A in foods derived from animals, fortified foods, or supplements (Whitney et al., 2011).  More than 1,000 times the nutritionally required amount can exceed the capacity of the liver to store and catabolize and will thus produce intoxication (Combs, 2012).

The condition attached to vitamin A toxicity is called hypervitaminosis A (Nix, 2012). It may be either acute or chronic. Acute toxicity usually follows a large single dose of vitamin A and is recognizes by symptoms suggesting an acute rise in intracranial pressure (McLaren and Kraemer, 2012). Acute symptoms may include; nausea, headache, fatigue, dizziness and loss of appetite. Chronic symptoms may include; dry skin, desquamation, cerebral edema, bone and joint pain, liver damage including cirrhosis, hemorrhages into the skin, and coma (Higdon and Drake, 2012). Natural beta-carotene, on the other hand, can be given for long periods of time virtually without risk of toxicity because the conversion of beta-carotene to active vitamin A is slow (Whitney et al., 2011). The only adverse effect of taking too much beta-carotene is the possibility of carotenemia, a harmless condition in which the skin turns a slight orange color (Lieberman et al., 2007). People take large doses of vitamin A with the aim of having improved vision, improved skin and resistance to disease. A pregnant woman who takes excess vitamin A is at a risk of miscarriages, or giving birth to a baby with malformations (Frankenburg, 2009). Too much vitamin A for a pregnant woman may disrupt a child’s brain cell activity. Vitamin A competes with vitamin D inside the body and therefore deprives the body of vitamin D creating a risk of osteoporosis (Asprey and Asprey, 2012).

 References

McDowell RL. Vitamins in Animal and human Nutrition.  2^nd ed. John Wiley & Sons. USA, Iowa; 2008

Combs GF. The Vitamins: Fundamental aspects in nutrition and health. 4^th ed. Elservier Inc. Sandiego CA USA, 2012

Lieberman S, Bruning N, Bruning NP. The real vitamin and mineral book: The definitive guide to designing your supplement program. 4^th ed. Penguin group New York, USA. 2007

Asprey L, Asprey D. The better baby book: How to have a healthier, smarter, happier baby. John Wiley & Sons, Inc., Hoboken , New Jersey, USA. 2012

Frankenburg RF.Vitamin discoveries and disasters: History, science and controversies. Greenwood Publishing group, Santa Barbara, California, USA

Whitney E, DeBruyne KL, Pinna K, Rolfes RS. Nutrition for health and health care. 4^th ed. Yolanda Cassio; Belmont, CA, USA. 2011

Higdon J, Drake JV. An evidence-based approach to vitamins and minerals: Health benefits and intake recommendations. 2^nd ed. Thiem; New York, NY, USA. 2011

Sizer F, Whitney E. Nutrition: Concepts and controversies. Wordsworth, Inc. 2013

Nix S. Williams’ basic nutrition and diet therapy. 14^th ed.  Missouri, USA. Elservier Health Sciences. 2012

McLaren DS, Kraemer K. Manual on Vitamin A deficiency Disorders (VADD). Karger. Basel, Switzerland; 2012.

Insel P, Ross D, McMahon K, Bernstein M. Discovering nutrition. 4^th ed. Jones & Barlett publishers, Burlington Ma USA, 2012.

Mcguire M, Beerman K, 2011. Nutritional Sciences. From fundamentals to food. 3^rd ed. Cengage learning

Desai BB. Handbook of nutrition and diet. Marcel Dekker, Inc. New York, Ny, USA. 2000.

Gibney JM, Margetts MB, Kearney MJ, Arab L. Public health nutrition. Blackwell Science. 2012

Ball GFM. Vitamins: Their role in the human body. Blackwell publishing company, 2008

Dryden GM. Animal nutrition science. CABI, Oxford UK, 2008

Stanfield PS, Hui YH. Nutrition and diet therapy: Self-instructional approaches. 5^th ed. Jones & Barlett publishers. USA, 2011

Seth SD, Seth V. Textbook of pharmacology. 3^rd ed. Elservier, India

Dente G, Hopkins JK. Macrobolic nutrition. Basic Health Publications, Inc. California USA. 2010

Elias J, Ketcham K. Chinese medicine for maximum immunity: Understanding the five elemental types for health and well-being. Random house LLC, 2007

Berdainer DC. Advanced nutrition micronutrients. CRC Press Boca Raton, Florida USA. 2010

GuoJ, Xiao B, Lou Y, Yan C, Zan l, Wang D, Zhao W. Antitumor effects of all-trans-retinoic acid on cultured human pancreatic cancer cells. J Gastroenterol Hepatol. 2006 21(2):443-8

Hulea AS. An introduction to vitamins, minerals and oxidative stress: the role of micronutrients and reactive oxygen species in normal and pathological processes. Universal Publishers, Boca Raton, Florida USA, 2008

Herrmann W, Obeid R. Vitamins in the prevention of human diseases. Deutsche nationalbibliothek, 2011

Shetty PS. Nutrition, immunity and infection. CABI publishers, Oxfordshire UK, 2010.

Gropper SAS, Smith LJ, Groff LJ. Advanced nutrition and human metabolism. 5^th ed. Wadsworth, Cengage learning. Bemont, CA, USA. 2009. 

Prasad NK. Bio-shield: Antioxidants against radiological, chemical and biological weapons. Strategic book publishing, New York, NY USA; 2008

Ito Y, Suzuki K, Ishii J, Hishida H, Tamakoshi A, Hamajima N, Aoki K. A population-based follow-up study on mortality from cancer or cardiovascular disease and serum carotenoids, retinol and tocopherols in Japanese inhabitants. Asian Pac J Cancer Prev. 2006 7 (4): 533-46

Heldman RD, Lund BD. Handbook of food engineering, second edition. 2^nd ed. CRC Press, Boca Raton, Florida USA, 2006.

Morley EJ, Thomas RD. Geriatric Nutrition. CRC Press, Taylor & Francis Group, Boca Raton, Florida USA; 2007

Sayo T, Sugiyama Y, Inoue S. Lutein, a non-provitamin A, activates the retinoic acid receptor to induce HAS3-dependent hyaluronan synthesis in keratinocytes. Bioscience, Biotechnology, and Biochemistry 2013, 77(6):1282-1286

Tanumihardjo AS. Carotenoids and human health.  Springer, New York, USA; 2012

Sommerburg O, Siems W, Kraemer K. Carotenoids and Vitamin A in translation medicine. CRC Press, Boca Ranton, FL; 2013

Messonnier Shawn. Natural health bible for dogs and cats. You’re a-Z guide to over 200 conditions, herbs, vitamins and supplements. Three Rivers Press, New York; 2010

World Health organization (WHO). Micronutrient deficiencies: Vitamin A deficiency. Accessed online from http://www.who.int/nutrition/topics/vad/en/ on 7/25/201

Semba DR, Bloem WM. Nutrition and health in developing countries. 2^nd ed. Springer,  New jersey, USA, 2008

 Bruning N, Lieberman S. The real vitamin and mineral book. The definitive guide to designing your personal supplement program. 4^th ed. Penguin, New York, USA; 2007

Hydrogenation, Fractionation and Interesterification

 Margarine Manufacture

A Brief on Margarine Manufacture

What is margarine: Margarine manufacture came to light in the 19th century as an alternative to butter. It was a popular substitute for people who could not afford butter or to whom butter wasn’t available. It can be made from either animal fat or plant oils. Most manufacturers prefer making margarine from plant oils because of their low values of saturated fatty acids especially Lauric, Myristic and Palmitic acid. Margarine plastic fats are normally produced by hydrogenation, fractionation, or interesterification.

Hydrogenation: During hydrogenation, unsaturated fatty acids are converted into saturated fatty acids in the presence of a suitable catalyst. After removal of impurities that may poison the catalyst, the oil (usually soybean or palm oil) are exposed to hydrogen gas at high pressures (2-10 atmospheres) and high temperatures (160-220⁰c). Finely divided nickel (divided to increase the surface area), at 0.01 – 0.2% serves as a catalyst. This process of hydrogenation occurs  due to isomerization of cis to trans configuration of fatty acid with the proportion of trans-fatty acids ranging between 5 – 40% in the final product.

Fractionation: This employs the mechanism of separation where the lipid is separated into solid and liquid fractions. It is usually employed in margarine manufacture from palm oil where the oil is separated into an olein and stearin fractions both of which have applications in certain margarine blends. Fractionation is limited by the sources of oils and varieties of products. 

Interesterification: Normally includes chemical interesterification and lipase-catalyzed interesterification.  In chemical interesterification, fully hydrogenated fats are blended with liquid oils as the feed-stocks usually using a lipid soluble catalyst (commonly sodium methoxide (0.1%)) at temperatures between 80⁰c to 120⁰c. Chemical interesterification randomizes the location of the different fatty acids, thereby improving the utility of the fat. Spreadability, melting point, and solid-fat content temperature profile are modified by the randomization. The chemical catalyst produces a darkening of the oil and some by-products, both of which need to be removed.

On the other hand, enzyme interesterification is a process in which a 1,3 specific lipase enzyme (from either bacterial, yeast and fungal sources) is used to catalyze the exchange of fatty acids attached to glycerol backbone of the fat in position 1 and 3 while leaving fatty acids in position 2 intact. It can achieve tailor-made fats which might have desired physical or nutritional properties unattainable by physical mixture or chemical randomization. Lipase-catalyzed interesterification conditions are mild and the process is more natural and green and would be better accepted by consumers. Enzymatic interesterification requires less severe reaction conditions; products are more easily purified, and it produces less waste than chemical interesterification. However it’s more expensive although prices for lipases are also gradually coming down, and lipase stability has been improved hence making the technology economically attractive.

References

O’Brien. R., 2009. Fats and Oils: Formulating and processing for applications. Richard D., 3^rd edition. ISBN 13: 978-1-4200-6166-6

Zhang. H, Xu. X, Mu. H, Nilsson. J, Adler-Nissen. J, Hoy. C., 2000. Lipozyme  IM-catalyzed Interesterification for the production of margarine fats in a 1 kg scale stirred tank reactor. Eur. J. Lipid Sci. Technol. 2000, 102, 411-418.

The American Oil Chemical Society Lipid Library, 2011. Edible oil processing-Modification. Enzymatic interesterification. Accessed online on January 22, 2013 from;  http://lipidlibrary.aocs.org/processing/enzinter/index.htm

 

Coultate TP. Food: The Chemistry of its components.  Fifth edition, Cabridge U.K; Royal Society of Chemistry; 2009.

Dietary fibre Consumption and Colorectal Cancer

Dietary fiber consumption and colorectal cancer

Colorectal cancer is cancer of the colon and rectum. It is a major cause of mortality and morbidity accounting for 9% of all cancer deaths worldwide (Haggar and Boushey, 2009). It is the third most commonly diagnosed cancer in males and second in females (Jemal et al., 2011) with 1.2 million new cases diagnosed in 2008 worldwide (American Cancer Society, 2013). In the United States, African Americans are at the highest risk of developing and dying from colon cancer whose incidence is also higher than in Africans living in Africa (O'Keefe et al., 2009). Intakes dietary fiber rich foods, red and processed meats along with alcohol abuse are currently the major suspected and highly researched dietary factors that are related to colorectal cancer (Aune et al., 2011). Colorectal cancer can be inherited including hereditary non-polyposis colorectal cancer due to genetic instability, and familial adenomatous polyposis coli due to a mutation in the adenomatous polyposis coli gene. The second type is due to inflammation including Crohns’ disease and ulcerative colitis and thirdly, sporadic which is mainly caused by lifestyle (Kraus and Arber, 2009).

Dietary fiber, colon, rectal and colorectal cancers defined

Dietary fiber is the indigestible carbohydrate that is fermented by colonic bacteria yielding short chain fatty acids such as acetate, propionate and butyrate (Scharlau et al., 2009). There are different constituents of dietary fiber that are of particular interest which include arabinoxylan, inulin, B-glucan, pectin, bran and resistant starches (Lattimer and Haub, 2010). High fiber foods include whole grain products and cereals, vegetables, fruits and legumes especially the skins of vegetable and fruits, berries and bran layers of grains. Dietary fiber may further be defined by whether it’s soluble or insoluble.

Colorectal cancer is known as cancer of the colon and rectum. It is the second leading cause of cancer deaths in America when cases in both men and women are combined. The colon also referred to as the large intestine is the lower part of the digestive system, which processes food for energy and rids the body of solid waste. Rectal cancer occurs in the last six inches of the large intestine (the rectum), otherwise if it occurs in the other part of the large intestine it is referred to as colon cancer. Together, these cancers are referred to as colorectal cancers (American cancer society, 2013)

Risk factors for colorectal cancer

The American Cancer Society defines a risk factor as something that affects your chance of getting a disease and further explains that having a risk factor or several risk factors doesn’t mean that you will get the disease (American Cancer Society, 2010).  Risk factors for colorectal cancer are hence identified to be: old age, personal history of colorectal cancer or polyps, personal history of inflammatory bowel disease, family history of colorectal cancer, inherited syndromes, racial and ethnic background, type 2 diabetes, lifestyle, diets low in fruits and vegetables, physical inactivity, smoking and alcohol abuse (Haggar et al, 2009).

Studies have shown relationships between various risk factors and colorectal cancer. An increased risk of colorectal cancer was associated with alcohol consumption where 30-45g of alcohol per day (equivalent to two to three alcoholic drinks per day) increases the risk by 16% and greater than 45g of alcohol per day is associated with 41% increased risk of colorectal cancer (Swimson and Seymour, 2012). 

Results from analysis of different cohort studies using meta-analysis showed that diabetic patients had a 20% higher colorectal cancer risk than non-diabetic patients. Smokers had a 16% higher risk of developing colorectal cancer than nonsmokers. The same study showed a 20% increased risk of developing colorectal cancer in individuals who consumed red and processed meats while no positive relationship was observed with increased fruit and vegetable consumption. Heavy physical inactivity indicated a 20% lower risk of developing colorectal cancer while obese individuals had a 40% increased risk of developing colorectal cancer than normal individuals while (Huxley et al., 2009). The incidence of colorectal polyps increased with increasing weight gain and waist hip ratio while waist circumference, adult height and BMI at age 18 were not associated with colorectal cancer (Wise et al., 2012).

Ulcerative colitis is associated with an increased risk of developing colorectal cancer while a variety of drugs including non-steroidal anti-inflammatory analgesics and hormonal replacement therapy have been associated with a reduced risk of colorectal cancer. A familial risk can be identified in up to 30% of CRC cases where Familial Adenomatous Polyposis (FAP) and Lynch syndrome are the two major hereditary conditions (Swimson and Seymour, 2012)

Diet, race and colorectal cancer

African Americans have a higher colon cancer incidence than Africans living in Africa probably because African Americans consume more red meat and saturated animal fat than Africans in Africa (O'Keefe et al., 2009). With diets high in red meat, the undigested carbohydrate in the colon is chiefly metabolized by hydrogen-producing bacteria which are latter colonized by secondary bile producing bacteria. With diets low in red meat but high in vegetables and fruits as in the case of Africans living in Africa, the undigested carbohydrate is fermented by methane producing bacteria which are latter colonized by lactobacilli species that promote mucosal health as do butyrate-producing firmicute (Uccello et al., 2012). The lactic acid producing bacteria in the colon include lactobacillus rhamnosus GG (LGG), Bifidobacterium lactis, and streptococcus thermophiles (Thomas and Greer, 2010). Red meat is a rich source of sulfur containing amino acids (methionine and cysteine) which form sulfate ions in the colon and rectum. Sulfate is used as an oxidant by sulfur reducing bacteria to degrade organic matter forming an equivalent amount of hydrogen sulfide per mole of sulfate reduced. Hydrogen sulfide generates free radicals, impairs cytochrome oxidase, suppresses butyrate utilization and inhibits the synthesis of mucus; all factors lead to mucosal insult, inflammation and ultimately colorectal cancer (Andrea Azcárate-Peril et al., 2011).

Colorectal cancer treatment, drug-nutrient interactions

In the United States, annual updates about occurrence and trends regarding cancer are provided by a collaborative effort from the National Cancer Institute (NCI), the Centers for Disease Control and Prevention (CDC), the North American Association of Central Cancer Registries (NAACCR) and the American Cancer Society (Edwards et al., 2010). According to the American Cancer Society, (2013) the main treatments for cancer include surgery, radiation therapy, chemotherapy and targeted therapy.

Chemotherapy for colorectal cancer

The American cancer society identifies the common chemotherapy drugs that are known to relieve colorectal cancer as Irinotecan (Campstosar), 5-Fluorouracil, Capecitabine (Xeloda) and Oxaliplatin (Eloxatin). These may be applied singly or as a combination depending on the cancer stage (American Cancer Society, 2013).  Research shows that less than 25% of colon cancer patients who undergo chemotherapy are responsive despite the prevalence and availability of early detection mechanisms (Meckling, 2006).

Drug-nutrient interactions for colorectal cancer

5-Fluorouracil (5-FU), is often given with the vitamin-like drug leucovorin (also called folinic acid), which makes it work better. Fluorouracil is an antimetabolite of the pyrimidine analog type. In the form of its active metabolite 5-FU inhibits the conversion of thiamine to TPP and inhibits DNA and RNA synthesis. The cofactor of transketolase, TPP promotes nucleic acid ribose synthesis and tumor cell proliferation through the non-oxidative transketolase (TK) pathway (Stargrove et al., 2008).

Studies supporting dietary fiber and colorectal cancer

Intakes of dietary fiber were significantly inversely associated with the risks of colorectal cancer when 4 to 7-day food diaries of participants were analyzed (Dahm et al., 2010). In a follow up study for 11 years based on total cereal, fruit, vegetable and fiber intakes as estimated from dietary questionnaires at baseline, total dietary fiber was inversely associated with colorectal cancer. This study employed multivariable adjustments for all other factors known to affect cancer initiation and progression leaving only dietary fiber as a treatment where an increase of 10g/day in dietary fiber intake was effected (Murphy et al., 2012). In reference to what particular sources of dietary fiber reduce carcinogenesis, studies showed that since dietary fibers differ in composition, they also differ in degree of protection against colorectal cancer for example wheat bran was effective in stimulating bacterial fermentation, oat bran had little effect and corn bran had no effect (Berg, 2001).

Mechanisms: dietary fiber rich foods in prevention of colorectal cancer

Prebiotics are non-digestible food ingredients that benefits the host by selectively stimulating the favorable growth and/or activity of one or more indigenous probiotic bacteria (Thomas and Greer, 2010). Currently all known prebiotics are oligosaccharides (carbohydrate compounds) known to resist digestion in the human small intestine and so reach the colon, where they are fermented by gut microflora. Oligosaccharides of interest include inulin, oligofructose, lactulose and resistant starch. Inulin and oligofructose are found in a variety of foods including chicory, onions, leeks, garlic, asparagus, bananas and articichokes. The bonds that connect the fructose subunits in both oligosaccharides cannot be cleaved by enzymes in the human intestines (Clark et al., 2012).

Dietary fiber (prebiotics) is fermented in the colon by gram-positive bacteria producing short chain fatty acids (SCFA) which are 2-carbon to 5-carbon weak acids, including acetate (C2), propionate (C3), butyrate (C4), and 5-carbon valerate (Canani et al., 2011). Butyrate is highly recognized for the potential to act on secondary chemoprevention by slowing growth and activating apoptosis in colon cancer cells. Additionally, SCFA can also act on primary prevention by activation of different drug metabolizing enzymes. This can reduce the burden of carcinogens and, therefore, decrease the number of mutations, reducing cancer risk (Scharlau et al., 2009). Dietary fiber increases stool bulk and stimulates intestinal transit thus reducing epithelial exposure to intraluminal carcinogens (Hawk and Mishra, 2012). Increased fiber increases water holding capacity and stool volume and dilutes any carcinogens or other toxicants that may be present in the colon. The larger, softer more fluid stool is easier to pass and is less abrasive. The faster transit time means that there is less time to interact with the colon wall or to produce secondary bile acids and other potential carcinogens (Salovaara et al., 2007).

Future directions in new research

Almost all the available information from prospective studies is based on less than 10 years of follow-up; some researchers believe that further evaluation of the effects of diet earlier in life and at longer intervals of observation is needed. A lot of literature relates intake of dietary fiber to reduction in colorectal cancer but still there are many studies that prove no relationship between the two. All the same, someone who is interested in reducing the risk of colorectal cancer should minimize intake of animal foods and increase intake of fruits and vegetables. Though fruits and vegetables may prove not to reverse the colorectal cancer, a higher fiber, low fat diet is likely to be beneficial not only protective.

References

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