1.1 Introduction
Zinc has been used since ancient Egyptian times to enhance wound healing, although the usefulness of this approach is only partially confirmed by the clinical data of today.
Zinc is necessary for the functioning of more than 300 different enzymes and plays a vital role in an enormous number of biological processes. Zinc is a cofactor for the antioxidant enzyme superoxide dismutase (SOD) and is in a number of enzymatic reactions involved in carbohydrate and protein metabolism.
Its immune-enhancing activities include regulation of T lymphocytes, CD4, natural killer cells, and interleukin II. In addition, zinc has been claimed to possess antiviral activity. It has been shown to play a role in wound healing, especially following burns or surgical incisions. Zinc is necessary for the maturation of sperm and normal fetal development. It is involved in sensory perception (taste, smell, and vision) and controls the release of stored vitamin A from the liver. Within the endocrine system, zinc has been shown to regulate insulin activity and promote the conversion thyroid hormones thyroxine to triiodothyronine.
Zinc deficiency affects about two billion people in the developing world and is associated with many diseases. Consumption of excess zinc can cause ataxia, lethargy and copper deficiency (Prasad, 2003)
Zinc is included in most single tablet over-the-counter daily vitamin and mineral supplements (DiSilvestro and Robert, 2004).
1.2 Triglycerides and cholesterol
If you just listen to the 'experts', you would think that cholesterol is an evil substance and that most of us would benefit from lowering our cholesterol as low as possible.
But it's not so. Cholesterol is a vitally important substance which is used for building our cell membranes and producing several of our hormones. If our cholesterol level drops too low, we are actually at increased risk for depression. (Psychosomatic Medicine 2000)
In most western country, atherosclerosis is the leading cause of illness and death. A high cholesterol level is an important modifiable risk factor for atherosclerosis. However, not all type of cholesterol increase the risk of atherosclerosis, a high level of LDL, ‘Bad’ cholesterol increase the risk, while a high level of HDH, ‘good’ cholesterol decrease the risk and a low level increase the risk.
Men tend to have noticeably lower HDL levels, with smaller size and lower cholesterol content, than women. Men also have an increased incidence of atherosclerotic heart disease.
Epidemiological studies have shown that high concentrations of HDL (over 60 mg/dL) have protective value against cardiovascular diseases such as ischemic stroke and myocardial infarction. Low concentrations of HDL (below 40 mg/dL for men, below 50 mg/dL for women) increase the risk for atherosclerotic diseases.
Data from the landmark Framingham Heart Study showed that, for a given level of LDL, the risk of heart disease increases 10-fold as the HDL varies from high to low. On the converse, however, for a fixed level of HDL, the risk increases 3-fold as LDL varies from low to high.
Even people with very low LDL levels are exposed to some increased risk if their HDL levels are not high enough (Bittner and Vera et al, 2007). LDL appears to be harmless until oxidized by free radicals, (Teissedre et al, 1996). It is postulated that ingesting antioxidants and minimizing free radical exposure may reduce LDL's contribution to atherosclerosis, though results are not conclusive. (Esterbauer et al, 1991)
1.3 Blood proteins
Blood proteins, also called serum proteins, are proteins found in blood plasma. Serum total protein in blood is 7g/dl, which in total makes 7% of total blood volume. They serve many different functions, including
Circulatory transport molecules for lipids, hormones, vitamins and metals
1.4 Objective of the study
The main aim of this research study is to determine the economical effect of dietary supplement of zinc on cholesterol level, as well as the effect on blood protein level.
CHAPTER TWO
LITERATURE REVIEW
2.1 ZINC
Zinc is an essential mineral that is naturally present in some foods, added to others, and available as a dietary supplement. Zinc is also found in many cold lozenges and some over-the-counter drugs sold as cold remedies.
Zinc is involved in numerous aspects of cellular metabolism. It is required for the catalytic activity of approximately 100 enzymes and it plays a role in immune function (Solomon et al, 1998), protein synthesis, wound healing, DNA synthesis, and cell division.
Zinc is involved in numerous aspects of cellular metabolism. It is required for the catalytic activity of approximately 100 enzymes and it plays a role in immune function (Solomon et al, 1998), protein synthesis, wound healing, DNA synthesis, and cell division.
Zinc also supports normal growth and development during pregnancy, childhood, and adolescence (Simmer et al, 1985) and is required for proper sense of taste and smell. A daily intake of zinc is required to maintain a steady state because the body has no specialized zinc storage system (Rink et al, 2000).
2.1.1 Recommended Intakes
Intake recommendations for zinc and other nutrients are provided in the Dietary Reference Intakes (DRIs) developed by the Food and Nutrition Board (FNB) at the Institute of Medicine of the National Academies (Institute of Medicine, Food and Nutrition Board, 2001).
DRI is the general term for a set of reference values used for planning and assessing nutrient intakes of healthy people. These values, which vary by age and gender, include the following:
Recommended Dietary Allowance (RDA): average daily level of intake sufficient to meet the nutrient requirements of nearly all (97%–98%) healthy individuals
Adequate Intake (AI): established when evidence is insufficient to develop an RDA and is set at a level assumed to ensure nutritional adequacy.
Tolerable Upper Intake Level (UL): maximum daily intake unlikely to cause adverse health effects.
The current RDAs for zinc are listed in Table 1. For infants aged 0 to 6 months, the FNB established an AI for zinc that is equivalent to the mean intake of zinc in healthy, breastfed infants.
Table 1: Recommended Dietary Allowances (RDAs) for Zinc (Institute of Medicine, Food and Nutrition Board, 2001)
Age
|
Male
|
Female
|
Pregnancy
|
Lactation
|
Birth to 6 months
|
2 mg*
|
2 mg*
| ||
7 months to 3 years
|
3 mg
|
3 mg
| ||
4 to 8 years
|
5 mg
|
5 mg
| ||
9 to 13 years
|
8 mg
|
8 mg
| ||
14 to 18 years
|
11 mg
|
9 mg
|
13 mg
|
14 mg
|
19+ years
|
11 mg
|
8 mg
|
11 mg
|
12 mg
|
Sources of Zinc
2.1.1.1 Food
A wide variety of foods contain zinc (Table 2) Oysters contain more zinc per serving than any other food, but red meat and poultry provide the majority of zinc in the American diet. Other good food sources include beans, nuts, and certain types of seafood (such as crab and lobster), whole grains, fortified breakfast cereals, and dairy products (Institute of Medicine, Food and Nutrition Board, 2001).
Table 2: Selected Food Sources of Zinc [U.S. Department of Agriculture,]
A wide variety of foods contain zinc (Table 2) Oysters contain more zinc per serving than any other food, but red meat and poultry provide the majority of zinc in the American diet. Other good food sources include beans, nuts, and certain types of seafood (such as crab and lobster), whole grains, fortified breakfast cereals, and dairy products (Institute of Medicine, Food and Nutrition Board, 2001).
Table 2: Selected Food Sources of Zinc [U.S. Department of Agriculture,]
Food
|
Milligrams (mg)
per serving |
Percent DV*
|
Oysters, 6 medium
|
76.7
|
513
|
Beef shanks, cooked, 3 ounces
|
8.9
|
59
|
Crab, Alaska king, cooked, 3 ounces
|
6.5
|
43
|
Pork shoulder, cooked, 3 ounces
|
4.2
|
28
|
Breakfast cereal fortified with 25% of the DV for zinc, ¾ cup serving
|
3.8
|
25
|
Chicken leg, roasted, 1 leg
|
2.7
|
18
|
Pork tenderloin, cooked, 3 ounces
|
2.5
|
17
|
Lobster, cooked, 3 ounces
|
2.5
|
17
|
Baked beans, canned, ½ cup
|
1.7
|
11
|
Cashews, dry roasted, 1 ounce
|
1.6
|
11
|
Yogurt, fruit, low fat, 1 cup
|
1.6
|
11
|
Raisin bran, ¾ cup
|
1.3
|
9
|
Chickpeas, ½ cup
|
1.3
|
9
|
Cheese, Swiss, 1 ounce
|
1.1
|
7
|
Almonds, dry roasted, 1 ounce
|
1.0
|
7
|
Milk, 1 cup
|
0.9
|
6
|
Chicken breast, roasted, ½ breast with skin removed
|
0.9
|
6
|
Cheese, cheddar or mozzarella, 1 ounce
|
0.9
|
6
|
Kidney beans, cooked, ½ cup
|
0.8
|
5
|
Peas, boiled, ½ cup
|
0.8
|
5
|
Oatmeal, instant, 1 packet
|
0.8
|
5
|
Flounder or sole, cooked, 3 ounces
|
0.5
|
3
|
* DV = Daily Value. DVs were developed by the U.S. Food and Drug Administration to help consumers compare the nutrient contents of products within the context of a total diet. The DV for zinc is 15 mg for adults and children age 4 and older. Food labels, however, are not required to list zinc content unless a food has been fortified with this nutrient. Foods providing 20% or more of the DV are considered to be high sources of a nutrient.
| ||
2.1.2 Dietary supplements
Supplements contain several forms of zinc, including zinc gluconate, zinc sulphate, and zinc acetate. The percentage of elemental zinc varies by form. For example, approximately 23% of zinc sulfate consists of elemental zinc; thus, 220 mg of zinc sulfate contains 50 mg of elemental zinc. The elemental zinc content appears in the Supplement Facts panel on the supplement container. Research has not determined whether differences exist among forms of zinc in absorption, bioavailability, or tolerability.
In addition to standard tablets and capsules, some zinc-containing cold lozenges are labeled as dietary supplements.
2.1.3 Other sources
Zinc is present in several products sold over the counter as natural medicines for colds, typically in the form of lozenges and nasal sprays and gels. Numerous case reports of anosmia (loss of smell), in some cases long-lasting or permanent, from the use of zinc-containing nasal gels or sprays (Alexander et al, 2006) raise questions about the safety of intranasal zinc. In June 2009, the FDA warned consumers to stop using three zinc-containing intranasal products because they might cause anosmia (U.S. Food and Drug Administration). The manufacturer has voluntarily withdrawn these products from the marketplace. These safety concerns do not apply to cold lozenges containing zinc.
Supplements contain several forms of zinc, including zinc gluconate, zinc sulphate, and zinc acetate. The percentage of elemental zinc varies by form. For example, approximately 23% of zinc sulfate consists of elemental zinc; thus, 220 mg of zinc sulfate contains 50 mg of elemental zinc. The elemental zinc content appears in the Supplement Facts panel on the supplement container. Research has not determined whether differences exist among forms of zinc in absorption, bioavailability, or tolerability.
In addition to standard tablets and capsules, some zinc-containing cold lozenges are labeled as dietary supplements.
2.1.3 Other sources
Zinc is present in several products sold over the counter as natural medicines for colds, typically in the form of lozenges and nasal sprays and gels. Numerous case reports of anosmia (loss of smell), in some cases long-lasting or permanent, from the use of zinc-containing nasal gels or sprays (Alexander et al, 2006) raise questions about the safety of intranasal zinc. In June 2009, the FDA warned consumers to stop using three zinc-containing intranasal products because they might cause anosmia (U.S. Food and Drug Administration). The manufacturer has voluntarily withdrawn these products from the marketplace. These safety concerns do not apply to cold lozenges containing zinc.
2.1.4 Zinc Intakes and Status
Most infants (especially those who are formula fed), children, and adults in the United States consume recommended amounts of zinc according to two national surveys, the 1988-1991 National Health and Nutrition Examination Survey (NHANES III) (Alaimo, 1994) and the 1994 Continuing Survey of Food Intakes of Individuals (CSFII).
However, some evidence suggests that zinc intakes among older adults might be marginal. An analysis of NHANES III data found that 35%–45% of adults aged 60 years or older had zinc intakes below the estimated average requirement of 6.8 mg/day for elderly females and 9.4 mg/day for elderly males. When the investigators considered intakes from both food and dietary supplements, they found that 20%–25% of older adults still had inadequate zinc intakes (Ervin, 2002).
Zinc intakes might also be low in older adults from the 2%–4% of U.S. households that are food insufficient (sometimes or often not having enough food) (Ribar, 2003). Data from NHANES III indicate that adults aged 60 years or older from food-insufficient families had lower intakes of zinc and several other nutrients and were more likely to have zinc intakes below 50% of the RDA on a given day than those from food-sufficient families (Dixon, 2001).
However, some evidence suggests that zinc intakes among older adults might be marginal. An analysis of NHANES III data found that 35%–45% of adults aged 60 years or older had zinc intakes below the estimated average requirement of 6.8 mg/day for elderly females and 9.4 mg/day for elderly males. When the investigators considered intakes from both food and dietary supplements, they found that 20%–25% of older adults still had inadequate zinc intakes (Ervin, 2002).
Zinc intakes might also be low in older adults from the 2%–4% of U.S. households that are food insufficient (sometimes or often not having enough food) (Ribar, 2003). Data from NHANES III indicate that adults aged 60 years or older from food-insufficient families had lower intakes of zinc and several other nutrients and were more likely to have zinc intakes below 50% of the RDA on a given day than those from food-sufficient families (Dixon, 2001).
2.1.5 Zinc Deficiency
Zinc deficiency is characterized by growth retardation, loss of appetite, and impaired immune function. In more severe cases, zinc deficiency causes hair loss, diarrhea, delayed sexual maturation, impotence, hypogonadism in males, and eye and skin lesions (Prasad, 2004).
Weight loss, delayed healing of wounds, taste abnormalities, and mental lethargy can also occur (Hambidge, 1989). Many of these symptoms are non-specific and often associated with other health conditions; therefore, a medical examination is necessary to ascertain whether a zinc deficiency is present.
Zinc nutritional status is difficult to measure adequately using laboratory tests due to its distribution throughout the body as a component of various proteins and nucleic acids (Van Wouwe, 1995).
Zinc nutritional status is difficult to measure adequately using laboratory tests due to its distribution throughout the body as a component of various proteins and nucleic acids (Van Wouwe, 1995).
Plasma or serum zinc levels are the most commonly used indices for evaluating zinc deficiency, but these levels do not necessarily reflect cellular zinc status due to tight homeostatic control mechanisms (Maret et al, 2006).
2.1.6 Groups at Risk of Zinc Inadequacy
When zinc deficiency does occur, it is usually due to inadequate zinc intake or absorption, increased losses of zinc from the body, or increased requirements for zinc (Prasad, 1996).
People at risk of zinc deficiency or inadequacy need to include good sources of zinc in their daily diets. Supplemental zinc might also be appropriate in certain situations.
2.1.6.1 People with gastrointestinal and other diseases
Gastrointestinal surgery and digestive disorders (such as ulcerative colitis, Crohn’s disease, and short bowel syndrome) can decrease zinc absorption and increase endogenous zinc losses primarily from the gastrointestinal tract and, to a lesser extent, from the kidney (Valberg et al, 1986 ). Other diseases associated with zinc deficiency include malabsorption syndrome, chronic liver disease, chronic renal disease, sickle cell disease, diabetes, malignancy, and other chronic illnesses. Chronic diarrhea also leads to excessive loss of zinc (Prasad, 2004).
2.1.6.1 People with gastrointestinal and other diseases
Gastrointestinal surgery and digestive disorders (such as ulcerative colitis, Crohn’s disease, and short bowel syndrome) can decrease zinc absorption and increase endogenous zinc losses primarily from the gastrointestinal tract and, to a lesser extent, from the kidney (Valberg et al, 1986 ). Other diseases associated with zinc deficiency include malabsorption syndrome, chronic liver disease, chronic renal disease, sickle cell disease, diabetes, malignancy, and other chronic illnesses. Chronic diarrhea also leads to excessive loss of zinc (Prasad, 2004).
2.1.6.2 Vegetarians
the bioavailability of zinc from vegetarian diets is lower than from non-vegetarian diets because vegetarians do not eat meat, which is high in bioavailable zinc and may enhance zinc absorption. In addition, vegetarians typically eat high levels of legumes and whole grains, which contain phytates that bind zinc and inhibit its absorption (Hunt, 2003).
the bioavailability of zinc from vegetarian diets is lower than from non-vegetarian diets because vegetarians do not eat meat, which is high in bioavailable zinc and may enhance zinc absorption. In addition, vegetarians typically eat high levels of legumes and whole grains, which contain phytates that bind zinc and inhibit its absorption (Hunt, 2003).
Vegetarians sometimes require as much as 50% more of the RDA for zinc than non-vegetarians. In addition, they might benefit from using certain food preparation techniques that reduce the binding of zinc by phytates and increase its bioavailability. Techniques to increase zinc bioavailability include soaking beans, grains, and seeds in water for several hours before cooking them and allowing them to sit after soaking until sprouts form (American Dietetic Association, 2003).
2.1.6.3 Pregnant and lactating women
Pregnant women, particularly those starting their pregnancy with marginal zinc status, are at increased risk of becoming zinc insufficient due, in part, to high fetal requirements for zinc (Caulfield et al, 1998 ).
2.1.6.3 Pregnant and lactating women
Pregnant women, particularly those starting their pregnancy with marginal zinc status, are at increased risk of becoming zinc insufficient due, in part, to high fetal requirements for zinc (Caulfield et al, 1998 ).
Lactation can also deplete maternal zinc stores. For these reasons, the RDA for zinc is higher for pregnant and lactating women than for other women (see Table 1).
2.1.6.4 Older infants who are exclusively breastfed
Breast milk provides sufficient zinc (2 mg/day) for the first 4–6 months of life but does not provide recommended amounts of zinc for infants aged 7–12 months, who need 3 mg/day. In addition to breast milk, infants aged 7–12 months should consume age-appropriate foods or formula containing zinc.
2.1.6.4 Older infants who are exclusively breastfed
Breast milk provides sufficient zinc (2 mg/day) for the first 4–6 months of life but does not provide recommended amounts of zinc for infants aged 7–12 months, who need 3 mg/day. In addition to breast milk, infants aged 7–12 months should consume age-appropriate foods or formula containing zinc.
Zinc supplementation has improved the growth rate in some children who demonstrate mild-to-moderate growth failure and who have a zinc deficiency (Brown et al, 1998).
2.1.6.5 People with sickle cell disease
Results from a large cross-sectional survey suggest that 44% of children with sickle cell disease have a low plasma zinc concentration, possibly due to increased nutrient requirements and/or poor nutritional status (Zemel et al, 2002).
2.1.6.5 People with sickle cell disease
Results from a large cross-sectional survey suggest that 44% of children with sickle cell disease have a low plasma zinc concentration, possibly due to increased nutrient requirements and/or poor nutritional status (Zemel et al, 2002).
Zinc deficiency also affects approximately 60%–70% of adults with sickle cell disease]. Zinc supplementation has been shown to improve growth in children with sickle cell disease (Prasad, 2002).
2.1.6.6 Alcoholics
Approximately 30%–50% of alcoholics have low zinc status because ethanol consumption decreases intestinal absorption of zinc and increases urinary zinc excretion (Prasad, 2002).
2.1.6.6 Alcoholics
Approximately 30%–50% of alcoholics have low zinc status because ethanol consumption decreases intestinal absorption of zinc and increases urinary zinc excretion (Prasad, 2002).
In addition, the variety and amount of food consumed by many alcoholics is limited, leading to inadequate zinc intake.
2.1.7 Zinc and Health
2.1.7.1 Immune function
Severe zinc deficiency depresses immune function , and even mild to moderate degrees of zinc deficiency can impair macrophage and neutrophil functions, natural killer cell activity, and complement activity. The body requires zinc to develop and activate T-lymphocytes. Individuals with low zinc levels have shown reduced lymphocyte proliferation response to mitogens and other adverse alterations in immunity that can be corrected by zinc supplementation (Wintergerst et al, 2007).
Severe zinc deficiency depresses immune function , and even mild to moderate degrees of zinc deficiency can impair macrophage and neutrophil functions, natural killer cell activity, and complement activity. The body requires zinc to develop and activate T-lymphocytes. Individuals with low zinc levels have shown reduced lymphocyte proliferation response to mitogens and other adverse alterations in immunity that can be corrected by zinc supplementation (Wintergerst et al, 2007).
2.1.7.2 Wound healing
Patients with chronic leg ulcers have abnormal zinc metabolism and low serum zinc levels, and clinicians frequently treat skin ulcers with zinc supplements (Anderson, 1995).
However, research has not shown that the general use of zinc sulfate in patients with chronic leg ulcers or arterial or venous ulcers is effective (Wilkinson et al, 1998).
2.1.7.3 Diarrhea
Zinc deficiency causes alterations in immune response that probably contribute to increased susceptibility to infections, such as those that cause diarrhea, especially in children (Wintergerst et al, 2007).
Studies show that poor, malnourished children in India, Africa, South America, and Southeast Asia experience shorter courses of infectious diarrhea after taking zinc supplements. The children in these studies received 4–40 mg of zinc a day in the form of zinc acetate, zinc gluconate, or zinc sulfate (Black, 1998).
The World Health Organization and UNICEF now recommend short-term zinc supplementation (20 mg of zinc per day, or 10 mg for infants under 6 months, for 10–14 days) to treat acute childhood diarrhea (World Health Organization and United Nations Children Fund, 2004).
2.1.7.3 Diarrhea
Zinc deficiency causes alterations in immune response that probably contribute to increased susceptibility to infections, such as those that cause diarrhea, especially in children (Wintergerst et al, 2007).
Studies show that poor, malnourished children in India, Africa, South America, and Southeast Asia experience shorter courses of infectious diarrhea after taking zinc supplements. The children in these studies received 4–40 mg of zinc a day in the form of zinc acetate, zinc gluconate, or zinc sulfate (Black, 1998).
The World Health Organization and UNICEF now recommend short-term zinc supplementation (20 mg of zinc per day, or 10 mg for infants under 6 months, for 10–14 days) to treat acute childhood diarrhea (World Health Organization and United Nations Children Fund, 2004).
2.1.7.4 Interactions with iron and copper
Iron-deficiency anemia is a serious world-wide public health problem. Iron fortification programs have been credited with improving the iron status of millions of women, infants, and children. Fortification of foods with iron does not significantly affect zinc absorption. However, large amounts of supplemental iron (greater than 25 mg) might decrease zinc absorption. Taking iron supplements between meals helps decrease its effect on zinc absorption (Whittaker et al, 1996).
High zinc intakes can inhibit copper absorption, sometimes producing copper deficiency and associated anemia (Willis et al, 2005). For this reason, dietary supplement formulations containing high levels of zinc sometimes contain copper.
2.1.8 Health Risks from Excessive Zinc
Zinc toxicity can occur in both acute and chronic forms. Acute adverse effects of high zinc intake include nausea, vomiting, loss of appetite, abdominal cramps, diarrhea, and headaches. One case report cited severe nausea and vomiting within 30 minutes of ingesting 4 g of zinc gluconate (570 mg elemental zinc) (Lewis et al, 1998).
Intakes of 150–450 mg of zinc per day have been associated with such chronic effects as low copper status, altered iron function, reduced immune function, and reduced levels of high-density lipoproteins (Lomaestro et al, 1995).
Reductions in a copper-containing enzyme, a marker of copper status, have been reported with even moderately high zinc intakes of approximately 60 mg/day for up to 10 weeks. The doses of zinc used in the AREDS study (80 mg per day of zinc in the form of zinc oxide for 6.3 years, on average) have been associated with a significant increase in hospitalizations for genitourinary causes, raising the possibility that chronically high intakes of zinc adversely affect some aspects of urinary physiology (Johnson et al , 2007).
The FNB has established upper intake levels for zinc (Table 3). Long-term intakes above the upper intake level increase the risk of adverse health effects. The upper intake levels do not apply to individuals receiving zinc for medical treatment, but such individuals should be under the care of a physician who monitors them for adverse health effects.
The FNB has established upper intake levels for zinc (Table 3). Long-term intakes above the upper intake level increase the risk of adverse health effects. The upper intake levels do not apply to individuals receiving zinc for medical treatment, but such individuals should be under the care of a physician who monitors them for adverse health effects.
Table 3: Tolerable Upper Intake Levels (U.L.s) for Zinc (Institute of Medicine, Food and Nutrition Board. 2001).
Age
|
Male
|
Female
|
Pregnant
|
Lactating
|
0 to 6 months
|
4 mg
|
4 mg
| ||
7 to 12 months
|
5 mg
|
5 mg
| ||
1 to 3 years
|
7 mg
|
7 mg
| ||
4 to 8 years
|
12 mg
|
12 mg
| ||
9 to 13 years
|
23 mg
|
23 mg
| ||
14 to 18 years
|
34 mg
|
34 mg
|
34 mg
|
34 mg
|
19+ years
|
40 mg
|
40 mg
|
40 mg
|
40 mg
|
2.1.8.1 Interactions with Medications
Zinc supplements have the potential to interact with several types of medications. A few examples are provided below. Individuals taking these medications on a regular basis should discuss their zinc intakes with their healthcare providers.
2.1.8.2 Antibiotics
Both quinolone antibiotics (such as Cipro®) and tetracycline antibiotics (such as Achromycin® and Sumycin®) interact with zinc in the gastrointestinal tract, inhibiting the absorption of both zinc and the antibiotic (Lomaestro et al, 1995). Taking the antibiotic at least 2 hours before or 4–6 hours after taking a zinc supplement minimizes this interaction.
2.1.8.3 Penicillamine
Zinc can reduce the absorption and action of penicillamine, a drug used to treat rheumatoid arthritis (Brewer et al 1993).
2.1.8.2 Antibiotics
Both quinolone antibiotics (such as Cipro®) and tetracycline antibiotics (such as Achromycin® and Sumycin®) interact with zinc in the gastrointestinal tract, inhibiting the absorption of both zinc and the antibiotic (Lomaestro et al, 1995). Taking the antibiotic at least 2 hours before or 4–6 hours after taking a zinc supplement minimizes this interaction.
2.1.8.3 Penicillamine
Zinc can reduce the absorption and action of penicillamine, a drug used to treat rheumatoid arthritis (Brewer et al 1993).
To minimize this interaction, individuals should take zinc supplements at least 2 hours before or after taking penicillamine.
2.1.8.4 Diuretics
Thiazide diuretics such as chlorthalidone (Hygroton®) and hydrochlorothiazide (Esidrix® and HydroDIURIL®) increase urinary zinc excretion by as much as 60% (Wester, 1980). Prolonged use of thiazide diuretics could deplete zinc tissue levels, so clinicians should monitor zinc status in patients taking these medications.
Thiazide diuretics such as chlorthalidone (Hygroton®) and hydrochlorothiazide (Esidrix® and HydroDIURIL®) increase urinary zinc excretion by as much as 60% (Wester, 1980). Prolonged use of thiazide diuretics could deplete zinc tissue levels, so clinicians should monitor zinc status in patients taking these medications.
2.1.9 Zinc and Healthful Diets
According to the 2005 Dietary Guidelines for Americans, "nutrient needs should be met primarily through consuming foods. Foods provide an array of nutrients and other compounds that may have beneficial effects on health. In certain cases, fortified foods and dietary supplements may be useful sources of one or more nutrients that otherwise might be consumed in less than recommended amounts. However, dietary supplements, while recommended in some cases, cannot replace a healthful diet."
The Dietary Guidelines for Americans describes a healthy diet as one that:
The Dietary Guidelines for Americans describes a healthy diet as one that:
Emphasizes a variety of fruits, vegetables, whole grains, and fat-free or low-fat milk and milk products
Whole grains and milk products are good sources of zinc. Many ready-to-eat breakfast cereals are fortified with zinc.
Includes lean meats, poultry, fish, beans, eggs, and nuts
Oysters, red meat, and poultry are excellent sources of zinc. Baked beans, chickpeas, and nuts (such as cashews and almonds) also contain zinc.
Is low in saturated fats, Trans fats, cholesterol, salt (sodium), and added sugars.
We Stays within your daily calorie needs.
2.2 Serum Protein
Serum proteins, also called blood protein, are protein found in blood plasma. Serum total protein in blood is 7g/dl, which in total makes 7% of total blood volume. They serve many different functions, including
Circulatory transport molecules for lipids, hormones, vitamins and metals
Enzymes complement components, protease inhibitor, and kinin precursors
Regulation of acellular activity and functioning and in the immune system
A total serum protein test measures the total amount of protein in the blood. It also measures the amounts of two major groups of proteins in the blood: albumin and globulin.
Albumin is made mainly in the liver. It helps keep the blood from leaking out of blood vessels. Albumin also helps carry some medicines and other substances through the blood and is important for tissue growth and healing.
Globulin is made up of different proteins called alpha, beta, and gamma types. Some globulins are made by the liver, while others are made by the immune system. Certain globulins bind with hemoglobin. Other globulins transport metals, such as iron, in the blood and help fight infection. Serum globulin can be separated into several subgroups by serum protein electrophoresis.
A test for total serum protein reports separate values for total protein, albumin, and globulin. The amounts of albumin and globulin also are compared (albumin/globulin ratio). Normally, there is a little more albumin than globulin and the ratio is greater than 1. A ratio less than 1 or much greater than 1 can give clues about problems in the body.
2.2.1 Why It Is Done
Albumin is tested to:
· Check how well the liver and kidney are working.
· Find out if your diet contains enough protein.
· Help determine the cause of swelling of the ankles (oedema) or abdomen (ascites) or of fluid collection in the lungs that may cause shortness of breath (pulmonary oedema).
Globulin is tested to:
· Determine your chances of developing an infection.
2.2.2 Results
A total serum protein test is a blood test that measures the amounts of total protein, albumin, and globulin in the blood. Results are usually available within 12 hours.
Normal
Table 4: Normal values may vary from lab to lab.
Blood protein
|
Normal level
|
%
|
Function
|
3.5-5.0 g/dl
|
60%
| ||
1.0-1.5 g/dl
|
18%
|
participate in immune system
| |
0.2-0.45 g/dl
|
4%
| ||
<1%
|
60% of plasma proteins are made up of the protein albumin, which are major contributors to osmotic pressure of plasma which assists in the transport of lipids and steroid hormones. Globulins make up 35% of plasma proteins and are used in the transport of ions, hormones and lipids assisting in immune function. 4% is fibrinogen which is essential in the clotting of blood and can be converted into insoluble fibrin.
Total proteins maybe elevated due to:
· Chronic infection (tuberculosis)
· Adrenal cortical hypo function
· Liver dysfunction
· Collagen vascular disease
· Leukemia
· Dehydration (diabetes acidosis, chronic diarrhea) etc
· Respiratory distress
Total protein maybe decreases due to:
· Malnutrition and absorption
· Liver disease
· Diarrhea
· Severe burns
· Loss through the urine in severe kidney disease
· Low albumin
· Low globulin
· Pregnancy
2.2.3 Serum Albumin
Albumin is negatively charge. The glomerular basement membrane is also negatively charge; some studies suggest that this prevent the filtration of albumin in urine. It is synthesized by the liver at a rate of 9-12g/day dietary protein intake; the normal serum albumin is 3.5-5.0g/dl
Being the major oncotic protein in health, it stands to reason that the rate of the production of albumin is controlled by changes in colloid osmotic pressure and osmolarity of vascular liver space. The capacity for increased production is fairly low (can only be increased by a factor or 2 or 3). Synthesis is increased by neuro-endocrine system, chiefly by insulin, thyroid hormone and cortical.
Albumin is catabolised at the rate of 9-13g/day (the same rate as it was produced) by pinocytosis in the cells adjacent to the vascular endothelium.
Although albumin perceived as in transvascular portion, the total intravascular amount by 30%.The ratio of albumin to water is, however, higher in the intravascular space (the extravascular fluid is 2/3 interstitial and 1/3 intravascular), hence the colloidal effect. Albumin cyclically leaves the circulation, through the endothelial barrier at the level of the lymph system via thoracic duct. During circulation half time of this process, is 16-18 hours. 4-5%of total intravascular albumin is lost this way per hour; this rate of movement is known as the transcapillary escape rate.
The most well-known type of albumin is serum albumin. It is most common in the blood or serum (providing its name) but it can also appear in other fluid compartments (providing the basis for the CSF/serum albumin ratio, for example.)
Serum albumin is the most abundant blood plasma protein and is produced in the liver and forms a large proportion of all plasma protein. The human version is human serum albumin, and it normally constitutes about 60% of human plasma protein.
Serum albumins are important in regulating blood volume by maintaining the oncotic pressure (also known as colloid osmotic pressure) of the blood compartment. They also serve as carriers for molecules of low water solubility this way isolating their hydrophobic nature, including lipid soluble hormones, bile salts, unconjugated bilirubin, free fatty acids (apoprotein), calcium, ions (transferrin), and some drugs like warfarin, phenobutazone, clofibrate & phenytoin.. Competition between drugs for albumin binding sites may cause drug interaction by increasing the free fraction of one of the drugs, thereby affecting potency.
2.2.3.1 Function of Serum Albumin
It is primary importance in maintaining the oncotic pressure of the blood (that is keeping the fluid from leaking out of the tissues).
The very small osmotic effect of plasma protein molecule produces an effective osmotic gradient across capillary membrane; this is known as the colloid osmotic or oncotic pressure. It is important factor opposing the net outward hydrostatic pressure. Albumin (molecular weight 6200) present intravascularly at significant concentration, and extravascularly at very low concentration because it cannot pass freely across the capillary wall, it is important protein contributing to the colloid.
Albumin level may be elevated in:
· Dehydration
· Congestive heart failure
· Possibly poor protein utilization
· Glucocorticoid excess
Albumin level maybe decrease in:
· Hypothyroidism
· Chronic debilitating
Specific types include:
· Bovine serum albumin (cattle serum albumin) or BSA often used in medical and molecular biology labs.
· Malnutrition- protein deficiency
· Dilution by excess water (drinking too much water, which is known as polydipsia or excess administration of intravascular fluids)
· Skin losses (burn, exfoliation dermatitis)
Low Albumin
Low albumin (hypoalbuminemia) may be caused by liver disease, nephrotic syndrome, burns, protein-losing enteropathy, malabsorption, malnutrition, late pregnancy, artefact, genetic variations and malignancy.
High Albumin
High albumin (hyperalbuminemia) is almost always caused by dehydration. In some cases of retinol (Vitamin A) deficiency the albumin level can become raised to High-normal values (ex: 4.9 g/dL). This is because retinol causes cells to swell with water (this is also the reason too much Vitamin A is toxic) (Gaull, 1984).
In lab experiments it has been shown that All-trans retinoic acid down regulates human albumin production (Suzuki, 2006).
Normal range of human serum albumin in adults (> 3 y.o.) is 3.5 to 5 g/dL. For children less than three years of age, the normal range is broader, 2.5-5.5 g/dL (Normal Ranges for Common Laboratory Tests Rush University)
2.2.3.2 Albumin Measurement
Plasma albumin is a component of the Liver Function Tests (LFTs) but may be ordered separately. Albumin can be measured in Serum (yellow-top tube), plain tube with no additives (red-top tube) or heparin plasma (green-top tube). The reference interval is 36 - 52 g/L. (note upper limit increased from 47 g/L),
2.2.4 Globulins
Globulins are compound of three fraction designated alpha, beta and gamma based on their electorpoietic motility. Sub fraction of alpha-globulin has been identified as well as a single fraction of each of the beta and gamma globulins. Most of the alpha and beta globulin are synthesized by the liver, whereas gamma globulin is produced by lymphocytes and plasma cells in the lymphoid tissues.
2.2.4.1 Alpha globulin
They consist of alpha-1 and alpha-2 globulins, alpha-1 includes alpha-1 antitrypsin, alpha-1 antychymotrypsin, orosomucoid (acid glycoprotein), serum amyloid A, and alpha-1 lipoprotein (HCL). Alpha-2 globulin includes alpha-2 macroglobulin (protease inhibitor). Haptoglobulin (bind free hemoglobulin), protein (inhibitor of activated coagulation factors FVIII and FV), ceruloplastin (carrier of copper) and alpha-2 lipoprotein
As concentration increases during inflammation, their measurement in the diagnosis and monitoring of many infectious diseases as well as other causes of acute and chronic infections
2.2.4.2 Beta globulin
They include carrier protein, complements ferritin, c-reactive proteins, beta lipoprotein and fibrinogen, transferring and many are also acute phase protein.
Beta globulin consists of beta-1 and beta-2 globulin including complement factor 3 and 4, c-reactive protein, plasminogen, beta-2 lipoprotein and some proportion of IgA (especially) and IgM. Fibrinogen also migrates to this region.
Increase in the beta globulin occurs in acute inflammation, hepatitis, malnutrition, and nephritic syndrome. Decrease occurs with hepatic insufficiency, severe inanition, blood loss and protein losing enteropathies.
2.2.4.3 Gamma globulin
They consist of hemoglobulins IgM, IgG and IgA In human and many other mammals. Most antibodies are in the gamma globulin fraction of blood. The human gamma globulin are administer (by injection) to persons lacking immunity either generally or to a particular disease after exposure.
Gamma globulin increase with ongoing antigenic stimulation often from infections agents. Broad increase (polyclonal gammopathies).Gamma globulins occur with acute or chronic inflammation, infection, chronic hepatitis, and immune regulatory disorder
Total proteins maybe elevated due to:
· Chronic infection (tuberculosis)
· Adrenal cortical hypo function
· Liver dysfunction
· Collagen vascular disease
· Leukemia
· Dehydration (diabetes acidosis, chronic diarrhea) etc
· Respiratory distress
Total protein maybe decreases due to:
· Malnutrition and absorption
· Liver disease
· Diarrhea
· Severe burns
· Loss through the urine in severe kidney disease
· Low albumin
· Low globulin
· Pregnancy
2.3 Lipids and lipoproteins
Lipids are water insoluble cellular component that can be extracted by non-polar solvent. Some lipids serve as structural component of membranes and other as storages forms of fuel. Several types of lipid are carried in plasma in relatively large amount cholesterol, triglycerides and phospholipids (Albert and Segrest, 1989).
It is only when hydrophobic lipids are bound to protein that they become soluble in the blood stream-lipoproteins. Lipoproteins are generally viewed as macromolecular complexes containing a core of lipid that carry hydrophobic plasma lipids particularly cholesterol and triglyceride in plasma.
Lipoproteins are spherical particles made up of hundreds of lipids and protein molecules (Ginsberg et al, 1992).
The lipid found in food is composed mainly of triglyceride, about 98%-99& of which 92%-95%n is fatty acid and the remainder is glycerol. The remaining 1%-2% of the lipids includes cholesterol, phospholipids, fat soluble vitamins, steroid, terpenes and mother fats.
The small amounts of unaponifable matter in food fat consist of steroids, fatty alcohols, hydrocarbons, pigment, glycerol esters and various other compounds, cholesterol occurs in all animal fats. Most sterols are cholesterol, but depending on the diet, other sterols such as phytosterol can make up an appreciable percentage of the total sterols particularly in people on vegetarian diet (Walker, 1991).
2.3.1 Cholesterol structure and properties
Cholesterol is a sterol (a combination of steroid and alcohol) and a lipid found in the cell membranes of all body tissues, and transported in the blood plasma of all animals (Hume, 1978).
By far the major sterol in animal tissues, cholesterol is amphipathic, with a polar head group and a non-polar head hydrocarbon body. Cholesterol was originally isolated from biliary calcus in 1969 by Pelletier de la sale.
Apart from the hydroxyl group at C3 and the double bond between C5 and C6 cholesterol is a fully saturated non polar hydrocarbon, insoluble in water and chemically unreactive and thus admirably suited to its role as a structural component of membranes (Myant, 1981).
Figure 1.1 Structure of cholesterol
2.3.2 Biological Functions of Cholesterol (Physiology)
Cholesterol contrary to its popular image as a potent enemy of health and longevity is actually a crucial substances that performs innumerable vital functions in the body (Hume et al, 1978).
Cholesterol is required to build and maintain membranes; it regulates membrane fluidity over the range of physiological temperatures. The hydroxyl group on cholesterol interacts with the polar head groups of the membrane phospholipids and sphingolipids, while the bulky steroid and the hydrocarbon chain are embedded in the membrane, alongside the nonpolar fatty acid chain of the other lipids. In this structural role, cholesterol reduces the permeability of the plasma membrane to protons (positive hydrogen ions) and sodium ions (Kaplan, 1963).
Within the cell membrane, cholesterol also functions in intracellular transport, cell signaling and nerve conduction. Recently, cholesterol has also been implicated in cell signaling processes, assisting in the formation of lipid rafts in the plasma membrane. In many neurons, a myelin sheath, rich in cholesterol, since it is derived from compacted layers of Schwann cell membrane, provides insulation for more efficient conduction of impulses. (Michael et al, 1996)
Within cells, cholesterol is the precursor molecule in several biochemical pathways. In the liver, cholesterol is converted to bile, which is then stored in the gallbladder. Bile contains bile salts, which solubilize fats in the digestive tract and aid in the intestinal absorption of fat molecules as well as the fat-soluble vitamins, Vitamin A, Vitamin D, Vitamin E, and Vitamin K. Cholesterol is an important precursor molecule for the synthesis of Vitamin D and the steroid hormones, including the adrenal gland hormones cortisol and aldosterone as well as the sex hormones progesterone, estrogens, and testosterone, and their derivatives.
Cholesterol is needed for the strength of bile acids which are essential for the absorption of fat and of many hormones s testosterone, estrogen, dihydoepiandrosterone, progesterone and cortical (Hume et al, 1978). Together with then sun exposure, cholesterol is required to produce vitamin D (Bouillon et al, 1995).
Cholesterol is also an essential element of cell membrane where it provides structural support and may even serve as a protective antioxidant (Girao, 1999).It also known to be very essential for conducting nervous impulse, especially at the level of the synapse.
2.3.3 Dietary sources
Animal fats are complex mixtures of triglycerides, with lesser amounts of phospholipids and cholesterol. As a consequence, all foods containing animal fat contain cholesterol to varying extents. Major dietary sources of cholesterol include cheese, egg yolks, beef, pork, poultry, and shrimp (Christie and William, 2003).
Human breast milk also contains significant quantities of cholesterol. Cholesterol is not present in plant-based food sources unless it has been added during the food's preparation (Jensen, 1978).
Total fat intake, especially saturated fat and Trans fat, plays a larger role in blood cholesterol than intake of cholesterol itself. Saturated fat is present in full fat dairy products, animal fats, and several types of oil and chocolate.
Trans-fat is most often encountered in margarine and hydrogenated vegetable fat, and consequently in many fast foods, snack foods, and fried or baked goods.
A change in diet in addition to other lifestyle modifications may help reduce blood cholesterol. Avoiding animal products may decrease the cholesterol levels in the body not through dietary cholesterol reduction alone but primarily through a reduced saturated fat intake. Those wishing to reduce their cholesterol through a change in diet should aim to consume less than 7% of their daily calories from saturated fat and less than 200 mg of cholesterol per day (National cholesterol education program, 2008).
2.3.4 Cholesterol Synthesis and Uptake
About 20–25% of total daily cholesterol production occurs in the liver; other sites of high synthesis rates include the intestines, adrenal glands, and reproductive organs. Synthesis within the body starts with one molecule of acetyl CoA and one molecule of acetoacetyl-CoA, which are dehydrated to form 3-hydroxy-3-methylglutaryl CoA (HMG-CoA). This molecule is then reduced to mevalonate by the enzyme HMG-CoA reductase. This step is an irreversible step in cholesterol synthesis and is the site of action for the statins (HMG-CoA Reductase Inhibitors).
Figure 1.2 Pathway of cholesterol synthesis
2.3.5 Maintenance of Cholesterol Homeostasis (Synthesis Regulation)
Normal healthy adult synthesis cholesterol at a rate of approximately 1g/day and consume approximately 0.3g/day. A relatively constant level of cholesterol in the body (150-200mg/dl) is maintained primarily by controlling the level of de novo synthesis. The level of cholesterol synthesis is regulated in part by the dietary intake of cholesterol (Michael, 1996), cholesterol from both diet and synthesis is utilized in the formation of membranes and in the synthesis of the steroid hormones and bile acid. The cellular supply of cholesterol is maintained at a steady level by three testing mechanisms.
1. Regulation of HMGR activity and levels
2. Regulation of excess intracellular free cholesterol through the activity of Acyl-COA: Cholestel acyl transferase, ACAT.
3, regulation of plasma cholesterol levels via LDL receptor –mediated uptake and LDL mediated reverse transport (Michael, 1996).
2.3.6 The utilization of cholesterol
Cholesterol is transport in the plasma predominantly as cholesteryl esters associated with lipoproteins. Dietary cholesterol is transported from the small intestine to the liver within chylomicrons. Cholesterol synthesized by the liver, as well as any dietary cholesterol in the liver that exceeds-VLDLs and these are converted to LDLs through the action of endothelial cell-associated lipoprotein lipase. Cholesterol found in plasma membranes can be extracted by HDLs and esterified by the HDL-associated enzyme LCAT. The cholesterol acquired from peripheral tissues by HDLs can then be transferred to VLDLs and LDLs via the action of cholesteryl ester transfer protein (Apo-D) which is associated with HDLs. Reverse cholesterol transport allows peripheral cholesterol to be return to the liver in LDLs. Ultimately, cholesterol is excreted in the bile as free cholesterol or as bile salts following conversion to bile acids in the liver.
2.3.7 Cholesterol Metabolism
Cholesterol is a member of a large class of biological compound called steroids that have similar structure. Cholesterol is present in all plasma lipoprotein but about 60% of the total cholesterol in plasma from a fasting human subject is carried in the LDL. One of the functions of LDL is to transport cholesterol in esterified form from the tissues to the liver. The esterified cholesterol formed on HDL is transported in to LDL and VLDL where it is incorporated into the non-polar core of the lipoprotein molecules. LDL carry its load of cholesteryl ester reaches the liver where the cholesteryl ester are hydrolyzed. The free cholesterol so formed enters the pool of free cholesterol in the hepatoate. This free cholesterol can leave the pool in the bile or after conversion into bile acids or by reincorporation into plasma lipoprotein (VLDL) (Kaplan, 1989)
 | |||
 | |||
2.3.8 Hypercholesterolemia
Hypercholesterolemia results from elevated level of fasting plasma total cholesterol and LDL in the blood even in the presence of normal levels of triglyceride (Ginsberg et al, 1992).
This disease process leads to myocardial infarction (heart attack), stroke, and peripheral vascular disease. Since higher blood LDL, especially higher LDL particle concentrations and smaller LDL particle size, contribute to this process more than the cholesterol content of the LDL particles (Brunzell et al, 2008).
LDL particles are often termed "bad cholesterol" because they have been linked to atheroma formation. On the other hand, high concentrations of functional HDL, which can remove cholesterol from cells and atheroma, offer protection and are sometimes referred to as "good cholesterol". These balances are mostly genetically determined but can be changed by body build, medications, food choices, and other factors (Durrington, 2003).
2.3.9 Hypocholesterolemia
Hypocholesterolemia can be seen in low total cholesterol concentration [<2.6mmol/L (<100mg/dl)]
This may be due to malnutrition, alcoholism, gastrointestinal disease and AIDS (Goldberg et al, 1993).
2.4 Plasma Lipoprotein-Structure and Function
The plasma lipoproteins are complex particles in which the lipid of plasma are carried in association with a variety of protein known as apoprotein (Albers, 1986) and hence have a key role in atherosclerotic cardiovascular disease. Plasma lipoproteins transport fats (Cholesterol and triglyceride) moving them from sites of absorption (intestines) to sites of storage. Their structure is highly suited to keeping lipids soluble in plasma.
Using the ultracentrifuge, one can separate the lipoprotein into chylomicrons, VLDL at a density below 1.006g/ml, LDL of density 1.006g/ml and 1.063g/ml and HDL of density 1.063-1.210g/ml. these lipoprotein classes correlate with electrophoresis pattern (Albers, 1986).
2.4.1 Low density lipoprotein
Low density lipoprotein is a type of lipoprotein that transports cholesterol and triglycerides from the liver to peripheral tissues. LDL is one of the five major groups of lipoproteins; these groups include chylomicrons, very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), low-density lipoprotein, and high-density lipoprotein (HDL), although some alternative organizational schemes have been proposed. Like all lipoproteins, LDL enables fats and cholesterol to move within the water-based solution of the blood stream. LDL also regulates cholesterol synthesis at these sites. It is used medically as part of a cholesterol blood test, and since high levels of LDL cholesterol can signal medical problems like cardiovascular disease, it is sometimes called "bad cholesterol," (as opposed to HDL, which is frequently referred to as "good cholesterol" or "healthy cholesterol")
2.4.1.1Transport into the cell
When a cell requires cholesterol, it synthesizes the necessary LDL receptors, and inserts them into the plasma membrane. The LDL receptors diffuse freely until they associate with clathrin-coated pits. LDL particles in the blood stream bind to these extracellular LDL receptors. The clathrin-coated pits then form vesicles that are endocytosed into the cell. After the clathrin coat is shed, the vesicles deliver the LDL and their receptors to early endosomes, onto late endosomes to lysosomes. Here the cholesterol esters in the LDL are hydrolyzed. The LDL receptors are recycled back to the plasma membrane.
2.4.1.2 Medical relevance
Because LDLs transport cholesterol to the arteries and can be retained there by arterial proteoglycans starting the formation of plaques, increased levels are associated with atherosclerosis, and thus heart attack, stroke, and peripheral vascular disease. For this reason, cholesterol inside LDL lipoproteins is often called "bad" cholesterol. This is a misnomer. The cholesterol transported on LDL is the same as cholesterol transported on other lipoprotein particles. The cholesterol itself is not "bad"; rather, it is how and where the cholesterol is being transported, and in what amounts over time, that causes adverse effects.
Increasing evidence has revealed that the concentration and size of the LDL particles more powerfully relates to the degree of atherosclerosis progression than the concentration of cholesterol contained within all the LDL particles. (Gary, 2007)
The healthiest pattern, though relatively rare, is to have small numbers of large LDL particles and no small particles. Having small LDL particles, though common, is an unhealthy pattern; high concentrations of small LDL particles (even though potentially carrying the same total cholesterol content as a low concentration of large particles) correlates with much faster growth of atheroma, progression of atherosclerosis and earlier and more severe cardiovascular disease events and death.
LDL is formed as VLDL lipoproteins lose triglyceride through the action of lipoprotein lipase (LPL) and become smaller and denser, containing a higher proportion of cholesterol.
A hereditary form of high LDL is familial hypercholesterolemia (FH). Increased LDL is termed hyperlipoproteinemia type II (after the dated Fredrickson classification).
LDL poses a risk for cardiovascular disease when it invades the endothelium and becomes oxidized, since the oxidized form is more easily retained by the proteoglycans. A complex set of biochemical reactions regulates the oxidation of LDL, chiefly stimulated by presence of free radicals in the endothelium.
2.4.1.3 Importance of Antioxidants
Because LDL appears to be harmless until oxidized by free radicals (Teissedre et al, 1996). It is postulated that ingesting antioxidants and minimizing free radical exposure may reduce LDL's contribution to atherosclerosis, though results are not conclusive (Esterbauer, 1991).
2.4.2 High density lipoprotein
High density lipoprotein that enable lipids like cholesterol and triglycerides to be transported within the water-based bloodstream, it begins in the liver and small intestine, as small protein rich particle that contain relatively little cholesterol and no cholesteryl ester. A high level of HDL-c seems to protect against cardiovascular diseases, and low HDL cholesterol level (less than40mg/dl or about 1mmol/L) increase the risk for heart disease. (American heart association, 2009) Cholesterol contained in HDL particles is considered beneficial for the cardiovascular health.
2.4.2.1 Structure
HDL is the smallest of the lipoprotein particles. They are the densest because they contain the highest proportion of protein. Their most abundant Apo lipoproteins are Apo A-I and Apo A-II (Després Jean-Pierre, 2009).
The liver synthesizes these lipoproteins as complexes of Apo lipoproteins and phospholipid, which resemble cholesterol-free flattened spherical lipoprotein particles. They are capable of picking up cholesterol, carried internally, from cells by interaction with the ATP-binding cassette transporter A1 (ABCA1). A plasma enzyme called lecithin-cholesterol acyltransferase (LCAT) converts the free cholesterol into cholesteryl ester (a more hydrophobic form of cholesterol), which is then sequestered into the core of the lipoprotein particle, eventually making the newly synthesized HDL spherical. They increase in size as they circulate through the bloodstream and incorporate more cholesterol and phospholipid molecules from cells and other lipoproteins, for example by the interaction with the ABCG1 transporter and the phospholipid transport protein (PLTP).
2.4.2.2 Function
HDL transports cholesterol mostly to the liver or steroid organs such as adrenals, ovary, and testes by direct and indirect pathways.
HDL carries many lipid and protein species, many of which have very low concentrations but are biologically very active. For example, HDL and their protein and lipid constituents help to inhibit oxidation, inflammation, activation of the endothelium, coagulation, and platelet aggregation.
Recommended range
Table:5 The American Heart Association, NIH and NCEP provides a set of guidelines for fasting HDL levels and risk for heart disease.(American Heart Association.2009)
Level mg/dL
|
Interpretation
| |
<40 for men, <50 for women
|
<1.03
|
Low HDL cholesterol, heightened risk for heart disease
|
40–59
|
1.03–1.55
|
Medium HDL level
|
>60
|
>1.55
|
High HDL level, optimal condition considered protective against heart disease
|
2.4.2.3 Diet and lifestyle
Certain changes in lifestyle can have a positive impact on raising HDL levels:
· Removing meat from the diet
· One drink of alcohol a day or less yields higher HDL-C levels, more so in women than men. HDL transports cholesterol to the liver and cholesterol is known to have a protective effect on the cell membrane. It is likely that this reflects the liver's need for more cholesterol to protect itself from the alcohol (Weidner et al, 1991).
· Increasing intake of cis-unsaturated fats and cholesterol, decreasing intake of trans-fats
· Avoiding supplements that contain omega 6 fish oil (omega 6 reduces cholesterol but does not discriminate between good and bad cholesterol) as well as limiting foods high in omega 6 (tilapia, most vegetable oils, nuts)
2.4.2.4 Drugs
Fibrates and niacin are the two pharmacological therapy uses to increase the level of HDL cholesterol.
2.4.3 Very low density lipoprotein
Very-low-density lipoprotein (VLDL) is a type of lipoprotein made by the liver. VLDL is one of the five major groups of lipoproteins (chylomicrons, VLDL, intermediate-density lipoprotein, low-density lipoprotein, high-density lipoprotein) that enable fats and cholesterol to move within the water-based solution of the bloodstream. VLDL is assembled in the liver from cholesterol and Apo lipoproteins. VLDL is converted in the bloodstream to low-density lipoprotein (LDL). VLDL particles have a diameter of 30-80 nm. VLDL transports endogenous products, whereas chylomicrons transport exogenous (dietary) products.
2.4.3.1 Function
VLDL transports endogenous triglycerides, phospholipids, cholesterol, and cholesteryl esters. It functions as the body's internal transport mechanism for lipids.
2.5 Triglycerides
Triglycerides are the most common type of fat found in the body. They are also a major energy source,
Which serves to be their primary function? Triglycerides are transported in the plasma in combination with other more polar lipids (phospholipids) and proteins as well as with cholesterol and cholesterol esters in complex lipoprotein macro molecules (Eisenberg, 1984).
2.5.1 Chemical structure
Most of the fats digested by humans are triglycerides. Triglycerides are formed from a single molecule of glycerol, combined with three molecules of fatty acid. The glycerol molecule has three hydroxyl (OH-) groups. Each fatty acid has a carboxyl group (COOH-). In triglycerides, the hydroxyl groups of the glycerol join the carboxyl groups of the fatty acid to form ester bonds.
The enzyme pancreatic lipase acts at the ester bond, hydrolyzing the bond and "releasing" the fatty acid. In triglyceride form, lipids cannot be absorbed by the duodenum. Fatty acids, monoglycerides (one glycerol, one fatty acid) and some diglycerides are absorbed by the duodenum, once the triglycerides have been broken down.
The chemical formula is RCOO-CH2CH (-OOCR') CH2-OOCR", where R, R', and R" are longer alkyl chains. The three fatty acids RCOOH, R'COOH and R"COOH can be all different, all the same, or only two the same.
Chain lengths of the fatty acids in naturally occurring triglycerides can be of varying lengths, but 16, 18 and 20 carbons are the most common. Natural fatty acids found in plants and animals are typically composed only of even numbers of carbon atoms due to the way they are bio-synthesized from acetyl CoA. Bacteria, however, possess the ability to synthesize odd- and branched-chain fatty acids. Consequently, ruminant animal fat contains odd numbered fatty acids, such as 15, due to the action of bacteria in the rumen.
Most natural fats contain a complex mixture of individual triglycerides. Because of this, they melt over a broad range of temperatures. Cocoa butter is unusual in that it is composed of only a few triglycerides, one of which contains palmitic, oleic, and stearic acids, in order of concentration.
Figure 2.1 General structure of Triglyceride
2.5.2 Triglycerides Metabolism
Triglyceride in the plasma at any given time is a balance between the rate of entry into the plasma and at the rate of removal, a change in either or both of these factors (Eisenberg, 1984).
2.5.2.1 In the intestine
Digestion in the intestinal lumen hydrolyses triglyceride into free fatty acids (FFA’s) and monoglyceride which are then eventually released into the lymphatics as triglyceride in chylomicrons. These lipids protein complexes contain about 82% triglyceride, 9% cholesterol (mainly as the ester), 7% phospholipids and a very small amount (less than 2%) of protein (Walker, 1991). An increased influx of chylomicrons triglyceride into the plasma occurs after the digestion of each meal, and this persists for several hours during which fat is absorbed. It causes an increase in plasma triglyceride concentrations.
2.5.2.2 In the liver
The liver is the second site form which triglyceride is release into the plasma. The source of the fatty acids present in the triglyceride entering the blood from this organ depends greatly on the nutritional state. Thus, in the fasting state, fatty acid derived from adipose cell triglyceride is taken up by the liver and a portion is re excreted as VLDL. Following a meal, dietary carbohydrate are taken up by the liver and converted to triglyceride which is secreted in the brain as lipoproteins.
2.5.3 Role in disease
A related term is "hyperglyceridemia" which refers to a high level of all glycerides, including monoglycerides, diglycerides and triglycerides.
In the human body, high levels of triglycerides in the bloodstream have been linked to atherosclerosis, and, by extension, the risk of heart disease and stroke. However, the relative negative impact of raised levels of triglycerides compared to that of LDL: HDL ratios is as yet unknown. The risk can be partly accounted for by a strong inverse relationship between triglyceride level and HDL-cholesterol level.
2.5.4 Guidelines
Table 6: The American Heart Association has set guidelines for triglyceride level (American Heart Association, 2009).
Interpretation
| ||
<150
|
<1.69
|
Normal range, low risk
|
150-199
|
1.70-2.25
|
Borderline high
|
200-499
|
2.26-5.65
|
High
|
>500
|
>5.65
|
Very high: high risk
|
Please note that this information is relevant to triglyceride levels as tested after fasting 8 to 12 hours. Triglyceride levels remain temporarily higher for a period of time after eating.
2.5.5 Reducing triglyceride levels
Diets high in carbohydrates, with carbohydrates accounting for more than 60% of the total caloric intake, can increase triglyceride levels (American Heart Association, 2009).
Increased exercise and reduced carbohydrate consumption ameliorate one potential cause of insulin overproduction to help maintain sensible triglyceride levels. Triglyceride levels are also reduced by omega-3 fatty acids from fish, flax seed oil and other sources.
It has been found that residents in Western countries do not ingest sufficient quantity of food with omega-3.
Heavy use of alcohol can elevate triglycerides levels (Hemat, 2003).