Digestion | September 8, 2015 | Author: The Super Pharmacist
Today, in most Western countries, the consumption of a diet high in processed food with limited nutritive value is thought to significantly contribute to a host of common chronic diseases including cardiovascular disease, hypertension, diabetes, and cancer.1 In contrast, high dietary intake of fruits, vegetables and whole grains is strongly associated with a reduced risk of developing these chronic illnesses which are the leading causes of death in Australia and in most industrialised nations.2, 3 In this context, increasingly health-conscious consumers are turning to nutraceuticals for their reported health benefits. The term, ‘nutraceuticals,’ covers the entire array of healthful nutritional products including functional foods, dietary supplements, and fortified foods (e.g. orange juice with added calcium).4 However, it is convenient to consider nutraceuticals as healthful products taken in dosage form (capsules, tinctures, or tablets) and functional foods as products consumed as foods and not in dosage form.5
Functional foods are generally defined as ‘any food or food ingredient that may provide a health benefit beyond the traditional nutrients it contains.’4 The term, ‘traditional nutrients’, refers to micronutrients such as vitamins, minerals, water, and macronutrients such as carbohydrates, proteins, and lipids (fats). Macronutrients provide the bulk energy that an organism's metabolic system needs to function while micronutrients provide the necessary co-factors for metabolism to be carried out. Vitamins, minerals, and water are compounds that are not produced by the body and are, therefore, essential to the diet. For example, vitamin C corrects the condition of ‘scurvy.’ Because it corrects a dietary deficiency, it is not an example of a functional food. However, soy, which contains soy protein, is associated with a reduced risk of cardiovascular disease. Because it is not essential to the human diet, it is considered to be a functional food. Other functional foods include red grapes and cranberry juice (for their proanthocyanidin content) and oat bran (for its fibre content) – health benefits attributed to ‘non-nutrient’ compounds4 – also called “phytochemicals." Functional foods range from fruits, vegetables, and whole grains, which are naturally high in phytochemicals, to products in which a specific ingredient is added, removed, increased, or decreased (e.g. orange juice that has been fortified with calcium for bone health). Proponents of functional foods say they promote optimal health and help reduce the risk of disease. In the US, the Food and Drug Administration (FDA) regulates the claims that manufacturers can make about the nutrient content of functional foods and their effects on disease, health or bodily function. The following is an example of an acceptable health claim: "Healthful diets with adequate folate may reduce a woman's risk of having a child with a brain or spinal cord defect."
The term, ‘dietary supplement,’ as defined in the US Dietary Supplement Health and Education Act (DSHEA) of 1994,6 is a product taken by mouth that contains a ‘dietary ingredient’ intended to supplement the diet. The dietary ingredients in these products may include: vitamins, minerals, herbs or other botanicals, amino acids, and substances such as enzymes, organ tissues, glandulars, and metabolites. In 2010, the US was the largest market for nutritional supplements, followed by Western Europe and Japan.7 Americans currently spend over $25 billion per year on more than 50,000 products containing vitamins and minerals, herbs and botanicals, and other ingredients such as glucosamine, fish oils, and probiotics. 8 Most countries place dietary supplements in a special category under the general umbrella of foods, not drugs. Federal law in the US does not require dietary supplements to be tested for safety or efficacy before they are marketed. As a result, the amount and quality of scientific evidence available to document the benefits of supplements varies widely. The FDA does, however, require that manufacturers guarantee the identity, purity, strength, and composition of their dietary supplements. The FDA may restrict the use of a supplement or remove it from the market if it is proven unsafe.9
In a landmark study published in 2004,10 researchers tracked 50 years in US Department of Agriculture food composition data for 13 nutrients in 43 garden crops, vegetables, strawberries and three melons. Comparison of data from 1950 to that of 1999 revealed statistically significant declines in the quantities of 6 essential nutrients: protein, calcium, phosphorus, iron, riboflavin (vitamin B2), and ascorbic acid (vitamin C). Authors attributed this decline of nutritional content to the increasing agricultural emphasis on improving crop ‘traits’ such as size, growth rate, and pest resistance with disregard of their nutrient content. Possibly the best evidence for conditions that warrant the use of nutraceuticals in the US comes from the Scientific Report of the 2015 Dietary Guidelines Advisory Committee (DGAC).11 The Committee characterised the following as shortfall nutrients in the American diet: vitamin A, vitamin D, vitamin E, vitamin C, folate, calcium, magnesium, fibre, and potassium. As of 2012, the Australian Institute of Health and Welfare (AIHW) has found that nutrients of potential concern for specific subpopulations in Australia include: calcium, vitamin D, iodine, folic acid, and iron.12 Iron deficiency is actually the most common and widespread nutritional disorder in the world. As well as affecting a large number of children and women in developing countries, it is the only nutrient deficiency which is also significantly prevalent in industrialised countries. A medically documented nutrient deficiency is a clear indication for the use of nutritional supplements. For example, a 2012 study found that nearly one-third of Australian adults over the age of 25 suffer from vitamin D deficiency.13 The prevalence of vitamin D deficiency increased significantly with age, was greater in women, in those of non-Europid origin, in the obese and those who were physically inactive and with a higher level of education. Nutrient intake recommendations are provided in the Dietary Reference Intakes (DRIs) developed by the US Food and Drug Nutrition Board.14 DRI is the general term for a set of reference values used to plan and assess nutrient intakes of healthy people. These values, which vary by age and gender, include:
DRIs are conveniently summarised in the form of tables for all of the following nutrients:15
After due consideration, the Working Party decided to adopt the approach of the US Dietary Reference Intakes but chose to alter select terminology, notably to retain the term, “Recommended Dietary Intake” (RDI).16 The various Nutrient Reference Values, as developed by the National Health and Medical Research Council (NHMRC), are summarised in the table below. Table 1. Nutrient Reference Values.16 [table id=28 /] In addition to the above mentioned essential nutrients, phytochemicals are non-nutritive plant chemicals that have protective or disease preventive properties. They are non-essential nutrients, meaning that they are not required by the human body for sustaining life. It is well-known that plants produce these chemicals to protect themselves but recent research demonstrate that they can also protect humans against diseases. There are more than a thousand known phytochemicals. Some of the well-known phytochemicals are lycopene in tomatoes, isoflavones in soy and flavanoids in fruits.17 Unlike the micronutrients (vitamins and minerals), the macronutrients (proteins, fats and carbohydrates) all contribute to dietary energy intake. A key component of the recommendation for macronutrients is how they are distributed in the diet; in other words, the percent of calories coming from protein, carbohydrate and fat. The DRIs express this distribution as the Acceptable Macronutrient Distribution Range or AMDR. The Acceptable Distribution Ranges for Adults (as a percentage of Calories) are as follows:
According to the US National Academy of Sciences, the AMDR is the range associated with reduced risk for chronic diseases, while providing essential nutrients like vitamins and minerals. People whose diet is outside the AMDR have the potential of increasing their risk of developing a disease of nutritional deficiency.18
When a food or drink is consumed, the nutrients that it contains are released from the matrix (surrounding substance), absorbed into the bloodstream and transported to specific target tissues. However, not all nutrients are utilised to the same extent. In other words, they differ in their ‘bioavailability.’ The FDA has defined bioavailability as the rate and extent to which active substances or therapeutic moieties contained in a drug are absorbed or become available at the site of action.19 This definition also applies to active substances (nutrients) present in food. The term, ‘bioaccessibility,’ refers to the first step of bioavailability. It is defined as the fraction of a compound which is released from its food matrix inside the gastrointestinal tract, and thereby, is made available for absorption.20 A large proportion of bioactive compounds remain poorly available after administration due to their low bioaccessibility which is compromised by factors such as low permeability and/or solubility within the gut, lack of stability during food processing, and lack of stability in the gastrointestinal tract due to factors such as acidity, enzymes, and the presence of other nutrients.21 Assuming that a nutrient is readily bioaccessible (i.e. effectively broken down in the gut and hence, available for absorption into the circulation), its subsequent bioavailability is dependent on both external and internal factors. External factors include the chemical form of the nutrient in question and/or its food matrix. Internal factors include gender, age, nutrient status and life stage (e.g. pregnancy).22
The chemical form of a nutrient is important. For example, most vitamins exist as multiple isomers. Isomers are molecules with the same molecular formula but with different three-dimensional configurations. Various isomers of the same vitamin have different clinical effects. Vitamin E, for instance, is made up a collection of 8 isomers (4 tocopherols and 4 tocotrienols), each of which has slightly different pharmacological activity in the body. Historically, only one of those eight isomers, d-alpha tocopherol, has been considered nutritionally significant and happens to be the only form of Vitamin E that currently has an established RDA to maintain optimal health.23 Alpha-tocopherol (which is more commonly found in supplements) and gamma-tocopherol (which is more commonly found in food sources) have different anti-inflammatory properties and vary in bioavailability.24
The surrounding substance within which a nutrient is embedded is called the “food matrix.” There is ample evidence that the physical state of the food matrix plays a key role in the stability, release, transfer, accessibility, and bioavailability of many food components.25, 26
Antioxidants are abundant compounds primarily found in fresh fruits and vegetables, and evidence for their role in the prevention of degenerative diseases is continuously emerging. However, the bioaccessibility and bioavailability of each compound differs greatly, and the most abundant antioxidants in ingested fruit are not necessarily those leading to the highest concentrations of active metabolites in target tissues.27 The limited bioavailability of antioxidants present in food from fruit and vegetable matrices is determined by their low bioaccessibility in the small intestine due to the physical and chemical interactions of the antioxidants with the indigestible polysaccharides of cell walls. Dietary fibre in the small intestine has been shown to reduce the rate (and in some cases. the extent) of release of antioxidants.27 Even if released during processing and digestion, antioxidants may interact with other food components in the gut by binding to macromolecules such as fibre and forming chemical complexes and colloidal structures that reduce or improve their bioavailability, a subject that needs urgent research.28
Folic acid is a B vitamin that is important for cell growth and metabolism. It is often added to breakfast cereals, flour and certain spreads, this added folic acid usually is more bioavailable than that naturally present in food, commonly referred to as dietary folate. Studies reported 20-70% lower bioavailability of dietary folate (from fruits, vegetables or liver) vs. synthetic folic acid.29
Carotenoids are powerful antioxidants that can help prevent some forms of cancer and heart disease. It is now recognised that carotenoids are not actively absorbed by the gut but are passively absorbed along with lipids (fats and oils).30 This may happen during food preparation and/or during the digestive process and may well be the single most important factor governing the rate and limit of their absorption. It is not surprising, therefore, to find greater bioavailability from heat-treated foods that have also been co-processed with oils.
Iron is a component of the protein molecule called haemoglobin. Haemoglobin is found in red blood cells and is responsible for carrying oxygen from the lungs to body tissues. Meat, fish and poultry, while containing highly bioavailable iron themselves, are also known to enhance the absorption of iron from all foods. Although this ‘meat factor’ has yet to be identified, an influence of the muscle protein has been suggested.31 Vitamin C is also a strong ‘helper,’ being able to increase iron absorption by two or three times.32 This means, for example, that having a glass of orange juice with a bowl of breakfast cereal helps the body use more of the iron in the cereal.
Vitamin C is an essential building block of collagen, the structural material for bone, skin, blood vessels and other tissue. It is also a potent antioxidant whereby it protects cells and their DNA from damage and prevents certain cancer-causing compounds from forming in the body. Evidence with regard to the bioavailability of vitamin C is contradictory. According to one group of investigators, vitamin C absorption is significantly higher when it is administered in the form of a citrus extract rather than as the isolated chemical compound itself (ascorbic acid).33 However, other studies have failed to demonstrate any difference in absorption between synthetic vitamin C and vitamin C supplied in the form of kiwi fruit,34, 35 or of vitamin C in supplement form administered in the presence or absence of a corn-based porridge,36 or of vitamin C in the form of oranges versus orange juice.37
Anthocyanins belong to a class of compounds called flavonoids. Anthocyanins are by far the most bioactive molecules carrying the strongest physiological effects of any plant compounds.38 Anthocyanins have powerful antioxidant and anti-inflammatory properties. Evidence suggests that the bioavailability of anthocyanins varies markedly depending on food matrices, including the degree to which other antioxidants and macronutrients are present in the food that is consumed.39
FoodMatrix® nutrients are available from Sportron™ and Grow Company. These supplements are alleged to be superior to other supplements on the market in terms of absorption and bioavailability based on their unique food matrices.40 More specifically, unlike all the other ‘isolated’ chemical USP (United States Pharmacopoeia) nutrients flooding the market, it is reported that individual FoodMatrix® nutrients are molecularly attached to unique protein chains. These nutrient-specific proteins transport and deliver their nutrient cargo to precise target sites. This is the mechanism whereby FoodMatrix® nutrients are reported to be better absorbed and more bioavailable than USP nutrients. The superior quality of FoodMatrix® nutrients is said to be supported by the work of molecular biologist, Dr. Gunter Bobel. In 1999, Bobel was awarded the Nobel Prize in Physiology for his work on protein transportation. Blobel's work indicates that proteins have "intrinsic signals" which act as "address tags" or "zip codes," directing proteins to particular sites. Peptide chains with particular amino acid sequences constitute these protein-specific signals. These signals determine whether a protein will pass through a membrane to a particular site within the cell (known as an organelle) or be exported out of the cell. Over 40 research articles are posted to the Sportron Targeted Nutrition website in support of contentions as to the superior bioavailability of FoodMatrix® products. The chief investigator in all but one of these studies is Professor Joe C. Vinson. Unfortunately, the technology whereby specific nutrients are chemically attached to protein carriers is said to be ‘proprietary,’ and thus, no independent research is available to corroborate any of the benefits attributed to FoodMatrix® nutrients. The health claims related to FoodMatrix® nutrients were tested in a court of law in the early 1990s. The $3 million lawsuit came to an out-of-court settlement when all parties agreed that the following claims can be made about FoodMatrix® nutrients: