Nutrition and Your Health
Nutrition science studies the relationship between diet and states of health and disease. Dieticians are Health professionals who are specialized in this area of expertise, highly trained to provide safe, evidence-based dietary advice and interventions. There is a spectrum ranging from malnutrition to optimal health, including many common symptoms and diseases which can often be prevented or alleviated with better nutrition.
Deficiencies, excesses and imbalances in diet can produce negative impacts on health, which may lead to diseases such as scurvy, obesity or osteoporosis, as well as psychological and behavioral problems. Moreover, excessive ingestion of elements that have no apparent role in health, (e.g. lead, mercury, PCBs, dioxins), may incur toxic and potentially lethal effects, depending on the dose. The science of nutrition attempts to understand how and why specific dietary aspects influence health.
Nutrition science seeks to explain metabolic and physiological responses of the body to diet. With advances in molecular biology, biochemistry, and genetics, nutrition science is additionally developing into the study of integrative metabolism, which seeks to connect diet and health through the lens of biochemical processes.
The human body is made up of chemical compounds such as water, amino acids (proteins), fatty acids (lipids), nucleic acids (DNA/RNA), and carbohydrates (e.g. sugars and fiber). These compounds in turn consist of elements such as carbon, hydrogen, oxygen, nitrogen, and phosphorus, and may or may not contain minerals such as calcium, iron, or zinc. Minerals ubiquitously occur in the form of salts and electrolytes. All of these chemical compounds and elements occur in various forms and combinations (e.g. hormones/vitamins, phospholipids, hydroxyapatite), both in the human body and in organisms (e.g. plants, animals) that humans eat. The human body necessarily comprises the elements that it eats and absorbs into the bloodstream. The digestive system, except in the unborn fetus, participates in the first step which makes the different chemical compounds and elements in food available for the trillions of cells of the body. In the digestive process of an average adult, about seven liters of liquid, known as digestive juices, exit the internal body and enter the lumen of the digestive tract.
The digestive juices help break chemical bonds between ingested compounds as well as modulate the conformation and/or energetic state of the compounds/elements. However, many compounds/ elements are absorbed into the bloodstream unchanged, though the digestive process helps to release them from the matrix of the foods where they occur. Any unabsorbed matter is excreted in the feces. But only a minimal amount of digestive juice is eliminated by this process; the intestines reabsorb most of it; otherwise the body would rapidly dehydrate; (hence the devastating effects of persistent diarrhea).
Study in this field must take carefully into account the state of the body before ingestion and after digestion as well as the chemical composition of the food and the waste. Comparing the waste to the food can determine the specific types of compounds and elements absorbed by the body. The effect that the absorbed matter has on the body can be determined by finding the difference between the pre-ingestion state and the post-digestion state. The effect may only be discernible after an extended period of time in which all food and ingestion must be exactly regulated and all waste must be analyzed. The number of variables (e.g. ‘confounding factors’) involved in this type of experimentation is very high. This makes scientifically valid nutritional study very time-consuming and expensive, and explains why a proper science of human nutrition is rather new.
In general, eating a variety of fresh, whole (unprocessed) plant foods has proven hormonally and metabolically favorable compared to eating a monotonous diet based on processed foods. In particular, consumption of whole plant foods slows digestion and provides higher amounts and a more favorable balance of essential and vital nutrients per unit of energy; resulting in better management of cell growth, maintenance, and mitosis (cell division) as well as regulation of blood glucose and appetite. A generally more regular eating pattern (e.g. eating medium-sized meals every 3 to 4 hours) has also proven more hormonally and metabolically favorable than infrequent, haphazard food intake.
Humans have evolved as omnivorous hunter-gatherers over the past 250,000 years. Early diets were primarily vegetarian with infrequent game meats and fish where available. Agriculture developed about 10,000 years ago in multiple locations throughout the world, providing grains such as wheat, rice, and maize, with staples such as bread and pasta. Farming also provided milk and dairy products, and sharply increased the availability of meats and the diversity of vegetables. The importance of food purity was recognized when bulk storage led to infestation and contamination risks. Cooking developed as an often ritualistic activity, due to efficiency and reliability concerns requiring adherence to strict recipes and procedures, and in response to demands for food purity and consistency.
Antiquity through Enlightenment
|c. 475 BC: Anaxagoras states that food is absorbed by the human body and therefore contained “homeomerics” (generative components), thereby deducing the existence of nutrients.|
|c. 400 BC: Hippocrates says, “Let food be your medicine and medicine be your food.”|
|The first recorded nutritional experiment is found in the Bible’s Book of Daniel. Daniel and his friends were captured by the king of Babylon during an invasion of Israel. Selected as court servants, they were to share in the king’s fine foods and wine. But they objected, preferring vegetables (pulses) and water in accordance with their Jewish dietary restrictions. The king’s chief steward reluctantly agreed to a trial. Daniel and his friends received their diet for 10 days and were then compared to the king’s men. Appearing healthier, they were allowed to continue with their diet.|
|1500s: Scientist and artist Leonardo da Vinci compared metabolism to a burning candle.|
|1747: Dr. James Lind, a physician in the British navy, performed the first scientific nutrition experiment, discovering that lime juice saved sailors who had been at sea for years from scurvy, a deadly and painful bleeding disorder. The discovery was ignored for forty years, after which British sailors became known as “limeys.” The essential vitamin C within lime juice would not be recognized by scientists until the 1930s.|
|1770: Antoine Lavoisier, the “Father of Nutrition and Chemistry” discovered the details of metabolism, demonstrating that the oxidation of food is the source of body heat.|
|1790: George Fordyce recognized calcium necessary for fowl survival.|
Modern era through 1941
|Early 1800s: The elements carbon, nitrogen, hydrogen and oxygen were recognized as the primary components of food, and methods to measure their proportions were developed.|
|1816: Francois Magendie discovers that dogs fed only carbohydrates and fat lost their body protein and died in a few weeks, but dogs also fed protein survived, identifying protein as an essential dietary component.|
|1840: Justus Liebig discovers the chemical makeup of carbohydrates (sugars), fats (fatty acids) and proteins (amino acids.)|
|1860s: Claus Bernard discovers that body fat can be synthesized from carbohydrate and protein, showing that the energy in blood glucose can be stored as fat or as glycogen.|
|Early 1880s: Kanehiro Takaki observed that Japanese sailors developed beriberi (or endemic neuritis, a disease causing heart problems and paralysis) but British sailors did not. Adding milk and meat to Japanese diets prevented the disease.|
|1896: Baumann observed iodine in thyroid glands.|
|1897: Christiaan Eijkman worked with natives of Java, who also suffered from beriberi. Eijkman observed that chickens fed the native diet of white rice developed the symptoms of beriberi, but remained healthy when fed unprocessed brown rice with the outer bran intact. Eijkman cured the natives by feeding them brown rice, discovering that food can cure disease. Over two decades later, nutritionists learned that the outer rice bran contains vitamin B1, also known as thiamine.|
|Early 1900s: Carl Von Voit and Max Rubner independently measure caloric energy expenditure in different species of animals, applying principles of physics in nutrition.|
|1906: Wilcock and Hopkins showed that the amino acid tryptophan was necessary for the survival of mice. Gowland Hopkins recognized “accessory food factors” other than calories, protein and minerals, as organic materials essential to health but which the body cannot synthesise.|
|1907: Stephen M. Babcock and Edwin B. Hart conduct the Single-grain experiment. This experiment runs through 1911.|
|1912: Casmir Funk coined the term vitamin, a vital factor in the diet, from the words “vital” and “amine,” because these unknown substances preventing scurvy, beriberi, and pellagra, were thought then to be derived from ammonia.|
|1913: Elmer V. McCollum discovered the first vitamins, fat soluble vitamin A, and water soluble vitamin B (in 1915; now known to be a complex of several water-soluble vitamins) and names vitamin C as the then-unknown substance preventing scurvy.|
|1919: Sir Edward Mellanby incorrectly identified rickets as a vitamin A deficiency, because he could cure it in dogs with cod liver oil.|
|1922: McCollum destroys the vitamin A in cod liver oil but finds it still cures rickets, naming vitamin D.|
|1922: H.M. Evans and L.S. Bishop discover vitamin E as essential for rat pregnancy, originally calling it “food factor X” until 1925.|
|1925: Hart discovers trace amounts of copper are necessary for iron absorption.|
|1927: Adolf Otto Reinhold Windaus synthesizes vitamin D, for which he won the Nobel Prize in Chemistry in 1928.|
|1928: Albert Szent-Gyorgyi isolates ascorbic acid, and in 1932 proves that it is vitamin C by preventing scurvy. In 1935 he synthesizes it, and in 1937 he wins a Nobel Prize for his efforts. Szent-Gyorgyi concurrently elucidates much of the citric acid cycle.|
|1930s: William Cumming Rose identifies essential amino acids, necessary proteins which the body cannot synthesize.|
|1935: Underwood and Marston independently discover the necessity of cobalt.|
|1936: Eugene Floyd Dubois shows that work and school performance are related to caloric intake.|
|1938: The chemical structure of vitamin E is discovered by Erhard Fernholz, and it is synthesized by Paul Karrer.|
|1941: The first Recommended Dietary Allowances (RDAs) were established by the National Research Council.|
|1992 The U.S. Department of Agriculture Introduces Food Guide Pyramid.|
|2002 Study shows relation between nutrition and violent behavior..|
|2005 Obesity may be caused by adenovirus in addition to bad nutrition.|
Nutrition and Health
There are six main nutrients in which the body needs to receive. These nutrients include carbohydrates, proteins, fats, vitamins, minerals, and water. It is important to consume these six nutrients on a daily basis to build and maintain healthy body systems.
Ill health can be caused by an imbalance of nutrients, producing either an excess or deficiency, which in turn affects body functioning cumulatively. Moreover, because most nutrients are, in some way or another, involved in cell-to-cell signalling (e.g. as building block or part of a hormone or signalling ‘cascades’), deficiency or excess of various nutrients affects hormonal function indirectly. Thus, because they largely regulate the expression of genes, hormones represent a link between nutrition and how our genes are expressed, i.e. our phenotype.
The strength and nature of this link are continually under investigation, but observations especially in recent years have demonstrated a pivotal role for nutrition in hormonal activity and function and therefore in health. One source of articles on nutrition and health is the quarterly newsletter of the Nutrition for Optimal Health Association (NOHA). Articles since 1984 are indexed by subject, name, and chronology.
Essential and non-essential amino acids
The body requires amino acids to produce new body protein (protein retention) and to replace damaged proteins (maintenance) that are lost in the urine. In animals amino acid requirements are classified in terms of essential (an animal cannot produce them) and non-essential (the animal can produce them from other nitrogen containing compounds) amino acids.
In addition to sufficient intake, an appropriate balance of essential fatty acids – omega-3 and omega-6 fatty acids – has been discovered to be crucial for maintaining health. Both of these unique “omega” long-chain polyunsaturated fatty acids are substrates for a class of eicosanoids known as prostaglandins which function as hormones. The omega-3 eicosapentaenoic acid (EPA) (which can be made in the body from the omega-3 essential fatty acid alpha-linolenic acid (LNA), or taken in through marine food sources), serves as building block for series 3 prostaglandins (e.g. weakly-inflammation PGE3). The omega-6 dihomo-gamma-linolenic acid (DGLA) serves as building block for series 1 prostaglandins (e.g. anti-inflammatory PGE1), whereas arachidonic acid (AA) serves as building block for series 2 prostaglandins (e.g. pro-inflammatory PGE 2). Both DGLA and AA are made from the omega-6 linoleic acid (LA) in the body, or can be taken in directly through food. An appropriately balanced intake of omega-3 and omega-6 partly determines the relative production of different prostaglandins, which partly explains the importance of omega-3/ omega-6 balance for cardiovascular health. In industrialized societies, people generally consume large amounts of processed vegetable oils that have reduced amounts of essential fatty acids along with an excessive amount of omega-6 relative to omega-3.
The rate of conversions of omega-6 DGLA to AA largely determines the production of the respective prostaglandins PGE1 and PGE2. Omega-3 EPA prevents AA from being released from membranes, thereby skewing prostaglandin balance away from pro-inflammatory PGE2 made from AA toward anti-inflammatory PGE1 made from DGLA. Moreover, the conversion (desaturation) of DGLA to AA is controlled by the enzyme delta-5-desaturase, which in turn is controlled by hormones such as insulin (up-regulation) and glucagon (down-regulation). Because different types and amounts of food eaten/absorbed affect insulin, glucagon and other hormones to varying degrees, not only the amount of omega-3 versus omega-6 eaten but also the general composition of the diet therefore determine health implications in relation to essential fatty acids, inflammation (e.g. immune function) and mitosis (i.e. cell division).
Several lines of evidence indicate lifestyle-induced hyperinsulinemia and reduced insulin function (i.e. insulin resistance) as a decisive factor in many disease states. For example, hyperinsulinemia and insulin resistance are strongly linked to chronic inflammation, which in turn is strongly linked to a variety of adverse developments such as arterial microinjuries and clot formation (i.e. heart disease) and exaggerated cell division (i.e. cancer).
Hyperinsulinemia and insulin resistance (the so-called metabolic syndrome) are characterized by a combination of abdominal obesity, elevated blood sugar, elevated blood pressure, elevated blood triglycerides, and reduced HDL cholesterol. The negative impact of hyperinsulinemia on prostaglandin PGE1/PGE2 balance may be significant.
The state of obesity clearly contributes to insulin resistance, which in turn can cause type 2 diabetes. Virtually all obese and most type 2 diabetic individuals have marked insulin resistance. Although the association between overfatness and insulin resistance is clear, the exact (likely multifarious) causes of insulin resistance remain less clear. Importantly, it has been demonstrated that appropriate exercise, more regular food intake and reducing glycemic load (see below) all can reverse insulin resistance in overfat individuals (and thereby lower blood sugar levels in those who have type 2 diabetes).
Obesity can unfavourably alter hormonal and metabolic status via resistance to the hormone leptin, and a vicious cycle may occur in which insulin/leptin resistance and obesity aggravate one another. The vicious cycle is putatively fuelled by continuously high insulin/leptin stimulation and fat storage, as a result of high intake of strongly insulin/leptin stimulating foods and energy.
Both insulin and leptin normally function as satiety signals to the hypothalamus in the brain; however, insulin/leptin resistance may reduce this signal and therefore allow continued overfeeding despite large body fat stores. In addition, reduced leptin signalling to the brain may reduce leptin’s normal effect to maintain an appropriately high metabolic rate.
There is debate about how and to what extent different dietary factors — e.g. intake of processed carbohydrates, total protein, fat, and carbohydrate intake, intake of saturated and trans fatty acids, and low intake of vitamins/minerals — contribute to the development of insulin- and leptin resistance. In any case, analogous to the way modern man-made pollution may potentially overwhelm the environment’s ability to maintain ‘homeostasis’, the recent explosive introduction of high Glycemic Index- and processed foods into the human diet may potentially overwhelm the body’s ability to maintain homeostasis and health (as evidenced by the metabolic syndrome epidemic).
Antioxidants are another recent discovery. As cellular metabolism/energy production requires oxygen, potentially damaging (e.g. mutation causing) compounds known as radical oxygen species or free radicals form as a result. For normal cellular maintenance, growth, and division, these free radicals must be sufficiently neutralized by antioxidant compounds, some produced by the body with adequate precursors (glutathione, Vitamin C in most animals) and those that the body cannot produce may only be obtained through the diet through direct sources (Vitamin C in humans, Vitamin A, Vitamin K) or produced by the body from other compounds (Beta-carotene converted to Vitamin A by the body, Vitamin D synthesized from cholesterol by sunlight). Different antioxidants are now known to function in a cooperative network, e.g. vitamin C can reactivate free radical-containing glutathione or vitamin E by accepting the free radical itself, and so on. Some antioxidants are more effective than others at neutralizing different free radicals.
Some cannot neutralize certain free radicals. Some cannot be present in certain areas of free radical development (Vitamin A is fat-soluble and protects fat areas, Vitamin C is water soluble and protects those areas). When interacting with a free radical, some antioxidants produce a different free radical compound that is less dangerous or more dangerous than the previous compound. Having a variety of antioxidants allows any byproducts to be safely dealt with by more efficient antioxidants in neutralizing a free radical’s butterfly effect.
Intestinal bacterial flora
Some information in this article or section has not been verified and may not be reliable. Please check for any inaccuracies, and modify and cite sources as needed. It is now also known that the human digestion system contains a population of a range of bacteria which are essential to digestion, and which are also affected by the food we eat. The role and significance of the intestinal bacterial flora is under investigation. Both good and bad bacteria inhabit the digestive system. It is estimated that in the Western world, most people are no longer in a homeostatic balance. It is ideal to have 80% good to 20% bad, typically differentiated by gram negative and gram positive staining, respectively; however, in western diets it is more likely to be the other way around. Consuming processed food that are low in nutrients and high in sugar will allow bad bacteria to flourish.
Blackberries are a source of polyphenol antioxidants. A growing area of interest is the effect upon human health of trace chemicals, collectively called phytochemicals, nutrients typically found in edible plants, especially colorful fruits and vegetables (see Whole Foods Diet, below). Unlike the anecdotal and sometimes specious nutritional claims of medicinal herbs and compounds, the effects of phytochemicals increasingly survive rigorous testing by prominent health organizations. One of the principal classes of phytochemicals are polyphenol antioxidants, chemicals which are known to provide certain health benefits to the cardiovascular system and immune system. These chemicals are known to down-regulate the formation of reactive oxygen species, key chemicals in cardiovascular disease.
Perhaps the most rigorously tested phytochemical is zeaxanthin, a yellow- pigmented carotenoid present in many yellow and orange fruits and vegetables. Repeated studies have shown a strong correlation between ingestion of zeaxanthin and the prevention and treatment of age-related macular degeneration (AMD). Less rigorous studies have proposed a correlation between zeaxanthin intake and cataracts. A second carotenoid, lutein, has also been shown to lower the risk of contracting AMD. Both compounds have been observed to collect in the retina when ingested orally, and they serve to protect the rods and cones against the destructive effects of light.
Another caretenoid, beta-cryptoxanthin, appears to protect against chronic joint inflammatory diseases, such as arthritis. While the association between serum blood levels of beta-cryptoxanthin and substantially decreased joint disease has been established, neither a convincing mechanism for such protection nor a cause-and-effect have been rigorously studied. Similarly, a red phytochemical, lycopene, has substantial credible evidence of negative association with development of prostate cancer.
The correlations between the ingestion of some phytochemicals and the prevention of disease are, in some cases, enormous in magnitude. For example, several studies have correlated high levels of zeaxanthin intake with roughly a 50% reduction in AMD. The difficulties in demonstrating causative properties and in applying the findings to human diet, however, are similarly enormous.
The standard for rigorous proof of causation in medicine is the double-blind study, a time-consuming, difficult and expensive process, especially in the case of preventative medicine. While new drugs must undergo such rigorous testing, pharmaceutical companies have a financial interest in funding rigorous testing and may recover the cost if the drug goes to market. No such commercial interest exists in studying chemicals that exist in orange juice and spinach, making funding for medical research difficult to obtain.
Even when the evidence is obtained, translating it to practical dietary advice can be difficult and counter-intuitive. Lutein, for example, occurs in many yellow and orange fruits and vegetables and protects the eyes against various diseases. However, it does not protect the eye nearly as well as zeaxanthin, and the presence of lutein in the retina will prevent zeaxanthin uptake.
Additionally, evidence has shown that the lutein present in egg yolk is more readily absorbed than the lutein from vegetable sources, possibly because of fat solubility. At the most basic level, the question “should you eat eggs?” is complex to the point of dismay, including misperceptions about the health effects of cholesterol in egg yolk, and its saturated fat content.
As another example, lycopene is prevalent in tomatoes (and actually is the chemical that gives tomatoes their red color). It is more highly concentrated, however, in processed tomato products such as commercial pasta sauce, or tomato soup, than in fresh “healthy” tomatoes. Such sauces, however, tend to have high amounts of salt, sugar, other substances a person may wish or even need to avoid.
Nutrition and sports
Some information in this article or section has not been verified and may not be reliable. Please check for any inaccuracies, and modify and cite sources as needed.
Nutrition is very important for improving sports performance. Contrary to popular belief, athletes need only slightly more protein than an average person. These needs are easily met by a balanced diet, and the recommended daily servings are generous enough to meet these needs. Additional protein intake is broken-down to be used as energy or stored as fat. Excess protein or grain consumption in the absence of alkalizing mineral intake (from fruits and vegetables) leads to chonic low grade acididosis in which calcium and glutamine are leached from bone and muscle respectively to keep the blood pH steady.
Endurance, strength and sprint athletes have different needs. Many athletes may require an increased caloric intake. Maintaining hydration during periods of physical exertion is key to good performance. While drinking too much water during activities can lead to physical discomfort, dehydration hinders an athlete’s ability. It is recommended that an athlete drink about 400-600mL 2-3 hours before activity, during exercise he or she should drink 150-350mL every 15 to 20 minutes and after exercise that he or she replace sweat loss by drinking 450-675 mL for every .5 Kg body weight loss during activity. Studies have shown that an athlete that drinks before they feel thirsty stays cooler and performs better than one who drinks on thirst cues.
Additional carbohydrates and protein before, during, and after exercise increase time to exhaustion as well as speed recovery. Dosage is based on work performed, lean body mass, and environmental factors (heat). The main fuel used by the body during exercise is carbohydrates, which is stored in muscle as glycogen- a form of sugar. During exercise, muscle glycogen reserves can be used up, especially when activities last longer than 90 min. When glycogen is not present in muscles, the muscle cells perform anaerobic respiration producing lactic acid, which is responsible for fatigue and burning sensation, and post exercise stiffness in muscles. Because the amount of glycogen stored in the body is limited, it is important for athletes to replace glycogen by consuming a diet high in carbohydrates. Meeting energy needs can help improve performance during the sport, as well as improve overall strength and endurance.
Nutrition and longevity
Lifespan may be somehow related to the amount of food energy consumed. A pursuit of this principle of caloric restriction followed, involving research into longevity of those who reduced their food energy intake while attempting to optimize their micro nutrient intake. Perhaps not surprisingly, some people found that cutting down on food reduced their quality of life so considerably as to negate any possible advantages of lengthening their lives. However, a small set of individuals persist in the lifestyle, going so far as to monitor blood lipid levels and glucose response every few months. See Calorie Restriction Society.
Underlying this research was the hypothesis that oxidative damage was the agent which accelerated aging, and that aging was retarded when the amount of carbohydrates (and thereby insulin release) was reduced through dietary restriction. However, recent research has produced increased longevity in animals (and shows promise for increased human longevity) through the use of insulin uptake retardation. This was done through altering an animal’s metabolism to allow it to consume similar food-energy levels to other animals, but without building up fatty tissue.
This has set researchers off on a line of study which presumes that it is not low food energy consumption which increases longevity. Instead, longevity may depend on an efficient fat processing metabolism, and the consequent long term efficient functioning of our organs free from the encumbrance of accumulating fatty deposits. Thus, longevity may be related to maintained insulin sensitivity. However, several other factors including low body temperature seem to promote longevity also and it is unclear to what extent each of them contribute. Antioxidants have recently come to the forefront of longevity studies which have included the Food and Drug Administration and Brunswick labs.
Whole Plant Food Diet
Heart disease, cancer, obesity, and diabetes are commonly called “Western” diseases because these maladies are rarely seen in developing countries. Research in China finds the difference may be nutritional; the Western diet includes consumption of large quantities of animal foods which could promote these observed diseases of affluence. One study found that rural Chinese eat mostly whole plant-based foods and “Western” diseases are rare; they instead suffer “diseases of poverty” which can be prevented by basic sanitation, health habits, and medical care.
In China “some areas have essentially no cancer or heart disease, while in other areas, they reflect up to a 100-fold increase.” Coincidentally, diets in China range from entirely plant-based to heavily animal-based, depending on the location. In contrast, diseases of affluence like cancer and heart disease are common throughout the United States. We observe large regional clusters of people in China (and other developing nations) who rarely suffer from these “Western” diseases possibly because their diets are rich in vegetables, fruits and whole grains.
The United Healthcare/Pacificare nutrition guideline recommends a whole plant food diet, as does a cover article of the issue of National Geographic (November 2005), titled The Secrets of LIVING LONGER. The latter is a lifestyle survey of three populations, Sardinians, Okinawans, and Adventists, who generally display longevity and “suffer a fraction of the diseases that commonly kill people in other parts of the developed world, and enjoy more healthy years of life. In sum, they offer three sets of ‘best practices’ to emulate. The rest is up to you.” In common with all three groups is to “Eat fruits, vegetables, and whole grains.”
The National Geographic article noted that a NIH funded study of 34,000 Seventh-Day Adventists between 1976 and 1988 “…found that the Adventists’ habit of consuming beans, soy milk, tomatoes, and other fruits lowered their risk of developing certain cancers. It also suggested that eating whole grain bread, drinking five glasses of water a day, and, most surprisingly, consuming four servings of nuts a week reduced their risk of heart disease. And it found that not eating red meat had been helpful to avoid both cancer and heart disease.”
The French paradox
It has been discovered that people living in Southern France live longer. Even though they consume a comparable amount of saturated fats, the rate of heart disease is lower in Southern France than in North America. A number of explanations have been suggested:
|Reduced consumption of processed carbohydrate and other junk foods;|
|Ethnic genetic differences allowing the body be harmed less by fats;|
|Regular consumption of red wine; or|
|Living in the South requires the body to produce less heat, allowing a slower, and therefore healthier, metabolic rate.|
Nutrition, industry and food processing
Since the Industrial Revolution some two hundred years ago, the food processing industry has invented many technologies that both help keep foods fresh longer and alter the fresh state of food as they appear in nature. Cooling is the primary technology that can help maintain freshness, whereas many more technologies have been invented to allow foods to last longer without becoming spoiled. These latter technologies include pasteurization, autoclavation, drying, salting, and separation of various components, and all appear to alter the original nutritional contents of food. Pasteurization and autoclavation (heating techniques) have no doubt improved the safety of many common foods, preventing epidemics of bacterial infection. But some of the (new) food processing technologies undoubtedly have downfalls as well.
Modern separation techniques such as milling, centrifugation, and pressing have enabled upconcentration of particular components of food, yielding flour, oils, juices and so on, and even separate fatty acids, amino acids, vitamins, and minerals. Inevitably, such large scale upconcentration changes the nutritional content of food, saving certain nutrients while removing others. Heating techniques may also reduce food’s content of many eat-labile nutrients such as certain vitamins and phytochemicals, and possibly other yet to be discovered substances. Because of reduced nutritional value, processed foods are often ‘enriched’ or ‘fortified’ with some of the most critical nutrients (usually certain vitamins) that were lost during processing. Nonetheless, processed foods tend to have an inferior nutritional profile than do whole, fresh foods, regarding content of both sugar and high GI starches, potassium/sodium, vitamins, fibre, and of intact, unoxidized (essential) fatty acids. In addition, processed foods often contain potentially harmful substances such as oxidized fats and trans fatty acids.
A dramatic example of the effect of food processing on a population’s health is the history of epidemics of beri-beri in people subsisting on polished rice. Removing the outer layer of rice by polishing it removes with it the essential vitamin thiamine, causing beri-beri. Another example is the development of scurvy among infants in the late 1800’s in the United States. It turned out that the vast majority of sufferers were being fed milk that had been heat-treated (as suggested by Pasteur) to control bacterial disease. Pasteurization was effective against bacteria, but it destroyed the vitamin C.
As mentioned, lifestyle- and obesity-related diseases are becoming increasingly prevalent all around the world. There is little doubt that the increasingly widespread application of some modern food processing technologies has contributed to this development. The food processing industry is a major part of modern economy, and as such it is influential in political decisions (e.g. nutritional recommendations, agricultural subsidizing). In any known profit-driven economy, health considerations are hardly a priority; effective production of cheap foods with a long shelf-life is more the trend.
In general, whole, fresh foods have a relatively short shelf-life and are less profitable to produce and sell than are more processed foods. Thus the consumer is left with the choice between more expensive but nutritionally superior whole, fresh foods, and cheap, usually nutritionally inferior processed foods. Because processed foods are often cheaper, more convenient (in both purchasing, storage, and preparation), and more available, the consumption of nutritionally inferior foods has been increasing throughout the world along with many nutrition-related health complications.
Most Governments provide guidance on good nutrition, and some also impose mandatory labeling requirements upon processed food manufacturers to assist consumers in complying with such guidance. Current dietary guidelines in the United States are presented in the concept of a food pyramid. There is no apparent consistency in science-based nutritional recommendations between countries, indicating the role of politics as well as cultural bias in research emphasis and interpretation.
Nutrition is taught in schools in many countries. In England and Wales the Personal and Social Education and Food Technology curriculums nutrition included, stressing the importance of a balanced diet and teaching how to read nutrition labels on packaging. But in developing countries, it is a distant dream; misconceptions, gender bias, unawareness about hygienic conditions etc. are still existing in their full strength.
Vitamins are nutrients required in very small amounts for essential metabolic reactions in the body. The term vitamin does not include other essential nutrients such as dietary minerals, essential fatty acids, or essential amino acids. Nor does the term refer to the large number of other nutrients that promote health, but are not strictly essential. Vitamins are biomolecules that act both as catalysts and substrates in chemical reactions. When acting as a catalyst, vitamins are bound to enzymes and are called cofactors, for example vitamin K forms part of the proteases involved in blood clotting. Vitamins also act as coenzymes to carry chemical groups between enzymes, for example folic acid carries various forms of carbon groups (methyl, formyl or methylene) in the cell.
Until the 1900s, vitamins were obtained solely through food intake. Many food sources contain different ratios of vitamins. Therefore, if the only source of vitamins is food, changes in diet will alter the types and amounts of vitamins ingested. However, as many vitamins can be stored by the body, short-term deficiencies (e.g. during a particular growing season) do not usually cause
disease. Vitamins have been produced as commodity chemicals and made widely available as inexpensive pills for several decades, allowing supplementation of the dietary intake.
The value of eating certain foods to maintain health was recognized long before vitamins were identified. The ancient Egyptians knew that feeding a patient liver would help cure night blindness, now known to be caused by a vitamin A deficiency. In 1747, the Scottish surgeon James Lind discovered that citrus foods helped prevent scurvy, a particularly deadly disease in which collagen is not properly formed, and is characterized by poor wound healing, bleeding of the gums, and severe pain. In 1753, Lind published his Treatise on the Scurvy, which recommended using lemons and limes to avoid scurvy, which was adopted by the British Royal Navy. This led to the nickname “Limey” for sailors of that organization. Lind’s discovery, however, was not widely accepted by individuals in the Royal Navy’s Arctic expeditions in the 19th century, where it was widely believed that scurvy could be prevented by practicing good hygiene, regular exercise, and by maintaining the morale of the crew while on board, rather than by a diet of fresh food. As a result, Arctic expeditions continued to be plagued by scurvy and other deficiency diseases. In the early 20th century, when Robert Falcon Scott made his two expeditions to the Antarctic the prevailing medical theory was that scurvy was caused by “tainted” canned food.
In 1881, Russian surgeon Nikolai Lunin studied the effects of scurvy while at the University of Tartu (in present day Estonia). He fed mice an artificial mixture of all the separate constituents of milk known at that time, namely the proteins, fats, carbohydrates, and salts. The mice that received only the individual constituents died, while the mice fed by milk itself developed normally. He made a conclusion that “a natural food such as milk must therefore contain, besides these known principal ingredients, small quantities of unknown substances essential to life”. However, his conclusions were rejected by other researchers when they were unable to reproduce his results. One difference was that he had used table sugar (sucrose), while other researchers had used milk sugar (lactose) which still contained small amounts of vitamin B.
In 1897, Christiaan Eijkman discovered that eating unpolished rice instead of the polished variety helped to prevent the disease beriberi. The following year, Frederick Hopkins postulated that some foods contained “accessory factors”—in addition to proteins, carbohydrates, fats, etc.—that were necessary for the functions of the human body. Hopkins was awarded the 1929 Nobel Prize for Physiology or Medicine, with Christiaan Eijkman, for their discovery of several vitamins.
Kazimierz Funk was the first to isolate the water-soluble complex of micronutrients, whose bioactivity Fletcher had identified, and Funk proposed the complex be named “Vitamine”. The name soon became synonymous with Hopkins’ “accessory factors”, and by the time it was shown that not all vitamins were amines, the word was already ubiquitous. In 1920, Jack Cecil Drummond proposed that the final “e” be dropped, to deemphasize the “amine” reference, after the discovery that vitamin C had no amine component.
Throughout the early 1900s, the use of deprivation studies allowed scientists to isolate and identify a number of vitamins. Initially, lipid from fish oil was used to cure rickets in rats, and the fat-soluble nutrient was called “antirachitic A”. The irony here is that the first “vitamin” bioactivity ever isolated, which cured rickets, was initially called “vitamin A”, the bioactivity of which is now called vitamin D; what we now call “vitamin A” was identified in fish oil because it was inactivated by ultraviolet light.
In 1931, Albert Szent-Gyorgyi and his research fellow Joseph Svirbely, determined that “hexuronic acid” was actually vitamin C and noted its anti-scorbutic activity, and 1937 Szent-Gyorgyi was awarded the Nobel Prize for his discovery. In 1943 Edward Adelbert Doisy and Henrik Dam were awarded the Nobel Prize for their discovery of vitamin K and its chemical structure.
Vitamins are classified as either water soluble, meaning that they dissolve easily in water, or fat soluble, and are absorbed through the intestinal tract with the help of lipids. Each vitamin is typically used in multiple reactions and therefore, most have multiple functions.
In humans there are thirteen vitamins, divided into two groups; four fat-soluble vitamins (A, D, E and K), and nine water-soluble vitamins (eight B vitamins and vitamin C):
|Vitamin B5||Pantothenic acid|
|Vitamin B7||Biotin Water|
|Vitamin B9||Folic acid|
|Vitamin C||Ascorbic acid|
|Vitamin D2–D4||Lumisterol, Ergocalciferol, Cholecalciferol,
|Vitamin E||Tocopherol, Tocotrienol|
Vitamins in nutrition and disease
Vitamins are essential for normal growth and development. Using the genetic blueprint inherited from its parents, a fetus begins to develop, at the moment of conception, from the nutrients it absorbs. The developing fetus requires certain vitamins and minerals to be present at certain times. These nutrients facilitate the chemical reactions that produce, among other things, skin, bone, and muscle. If there is serious deficiency in one or more of these nutrients, a child may develop a deficiency disease. Even minor deficiencies have the potential to cause permanent damage.
For the most part, vitamins are obtained through food sources. However, a few vitamins are obtained by other means: for example, microorganisms in the intestine – commonly known as “gut flora” – produce vitamin K and biotin, while one form of vitamin D is synthesized in the skin with the help of natural ultraviolet in sunlight. Some vitamins can be obtained from precursors that are obtained in the diet. Examples include vitamin A, which can be produced from beta carotene and niacin, from the amino acid tryptophan. Once growth and development are completed, vitamins remain essential components of the healthy maintenance of the cells, tissues, and organs that make up the human body, and enable the body to efficiently use the calories provided by the food that we eat, and to help process proteins, carbohydrates, and fats.
Deficiencies of vitamins are classified as either primary or secondary. A primary deficiency occurs when you do not get enough of the vitamin in the food you eat. A secondary deficiency may be due to an underlying disorder that prevents or limits the absorption or use of the vitamin, due to a “lifestyle factor”, such as smoking, excessive alcohol consumption, or the use of medications that interfere with the absorption or the body’s use of the vitamin. Individuals who eat a varied diet are unlikely to develop a severe primary vitamin deficiency. Whereas, restrictive diets have the potential to cause prolonged vitamin deficits, which may result in often painful and potentially deadly diseases.
Because most vitamins are not stored in the body, a person must consume them regularly to avoid deficiency. Body stores for different vitamins vary widely; vitamins A, D, and B12 are stored in significant amounts in the body, mainly in the liver, and an adult may be deficient in vitamin A and B12 for long periods of time before developing a deficiency condition. Vitamin B3 is not stored in the body in significant amounts, and stores may only last a couple of weeks. Well-known vitamin deficiencies involve thiamine (beriberi), niacin (pellagra), vitamin C (scurvy) and vitamin D (rickets). In much of the developed world, such deficiencies are rare due to; an adequate supply of food and the addition of vitamins and minerals, often called fortification, to common foods.
Mineral and/or vitamin deficiency or excess may yield symptoms of diminishing health such as goiter, scurvy, osteoporosis, weak immune system, disorders of cell metabolism, certain forms of cancer, symptoms of premature aging, and poor psychological health (including eating disorders), among many others. As of 2005, twelve vitamins and about the same number of minerals are recognized as “essential nutrients”, meaning that they must be consumed and absorbed – or, in the case of vitamin D, alternatively synthesized via UVB radiation – to prevent deficiency symptoms and death. Certain vitamin-like substances found in foods, such as carnitine, have also been found essential to survival and health, but these are not strictly “essential” to eat because the body can produce them from other compounds. Moreover, thousands of different phytochemicals have recently been discovered in food (particularly in fresh vegetables), which have many known and yet to be explored properties including antioxidant activity . Other essential nutrients include essential amino acids, choline and the essential fatty acids.
Vitamin side effects and overdose
In large doses some vitamins have documented side effects. Vitamin side effects tend to increase in severity with increasing dosage. The likelihood of consuming too much of any vitamin from food is remote, but overdosing from vitamin supplementation does occur. At high enough dosages some vitamins cause side effects, such as nausea, diarrhea, and vomiting. Unlike some of the side effects caused by drugs, vitamin side effects rarely cause any permanent harm. When vitamin side effects emerge, recovery is often accomplished by reducing the dosage. Furthermore, the concentrations of vitamins an individual can tolerate vary widely, and appear to be related to age and state of health. It is for these reasons that physicians and scientists carefully review the clinical data on supplement use in order to determine upper dosage thresholds for each vitamin that can be tolerated as a daily dose by the entire population without side effects. This dosage is known as the tolerable upper intake level (UL).
Dietary supplements, often containing vitamins, are used to ensure that adequate amounts of nutrients are obtained on a daily basis, if optimal amounts of the nutrients cannot be obtained through a varied diet. Scientific evidence supporting the benefits of some dietary supplements is well established for certain health conditions, but others need further study.
Supplements are, as required by law, not intended to treat, diagnose, mitigate, prevent, or cure disease. In some cases, dietary supplements may have unwanted effects, especially if taken before surgery, with other dietary supplements or medicines, or if the person taking them has certain health conditions. Vitamin supplements may also contain levels of vitamins many times higher, and in different forms, than one may ingest through food. Before taking a supplement, it is important to check with a knowledgeable health care provider, especially when combining or substituting supplements with other foods or medicine.
Governmental regulation of vitamin supplements
Most countries place dietary supplements in a special category under the general umbrella of “foods,” not drugs. This necessitates that the manufacturer, and not the government, be responsible for ensuring that its dietary supplement products are safe before they are marketed. Unlike drug products, that must implicitly be proven safe and effective for their intended use before marketing, there are often no provisions to “approve” dietary supplements for safety or effectiveness before they reach the consumer. Also unlike drug products, manufacturers and distributors of dietary supplements are not generally required to report any claims of injuries or illnesses that may be related to the use of their products however, side effects have been reported for several types of vitamin supplements.
Vitamin poisoning, or hypervitaminosis, refers to a condition of high storage levels of vitamins, which can lead to toxic symptoms. The medical names of the different conditions are derived from the vitamin involved: an excess of vitamin A, for example, is called “hypervitaminosis A”. High dosage vitamin A, high dosage, slow release vitamin B3 and very high dosage vitamin B6 alone, i.e. without vitamin B complex, are sometimes associated with vitamin side effects that usually rapidly cease with supplement reduction or cessation. Conversely, certain vitamins do not produce toxicity in excess levels. Vitamin C has been used in dosages over 100,000 mg for serious illness — over 1000 times the daily recommended intake — without ill effects. However, Vitamin C does have a pronounced laxative effect, typically when intake of vitamin C is in the range of 5-20 grams per day for a person in normal “good health”.
High doses of mineral supplements can also lead to side effects and toxicity. Mineral-supplement poisoning does occur occasionally due to excessive and unusual intake of iron-containing supplements, including some multivitamins. Hypervitaminosis with multivitamins is uncommon.
Dietary minerals are the chemical elements required by living organisms, other than the four elements Carbon, Hydrogen, Nitrogen, and Oxygen which are ubiquitous in organic molecules. They can be either bulk minerals (required in relatively large amounts) or trace minerals (required only in very small amounts).
These can be naturally occurring in food or added in elemental or mineral form, such as calcium carbonate or sodium chloride. Some of these additives come from natural sources such as ground oyster shells. Sometimes minerals are added to the diet separately from food, as vitamin and mineral supplements and in dirt eating, called pica or geophagy.
Appropriate intake levels of each dietary mineral must be sustained to maintain physical health. Excessive intake of a dietary mineral may either lead to illness directly or indirectly because of the competitive nature between mineral levels in the body. For example, large doses of zinc are not really harmful unto themselves, but will lead to a harmful copper deficiency (unless compensated for, as in the Age-Related Eye Disease Study). Soils in different geographic areas contain varying quantities of minerals.
In Human nutrition, the dietary bulk mineral elements (RDA > 200 mg/day) are (in alphabetical order):
The most important trace mineral elements (RDA < 200 mg/day) are (again, in alphabetical order):
Iodine is required in larger quantities than the other trace minerals in this list and is sometimes counted with the bulk minerals. Sodium is not generally found in dietary supplements, despite being needed in large quantities, because the mineral is so common in food. This list is not an endorsement of the need of any of these minerals as dietary supplements.
Many other minerals have been suggested as required in human nutrition, in varying quantities. Standards of evidence vary for different elements, and not all have been definitively established as essential to human nutrition. Common candidates include:
(elements for which convincing scientific evidence is lacking are marked as suspect)
|Tungsten (some organisms use tungsten rather than molybdenum)|
Various other elements found in food supplies may vary from holding no known nutritional value (such as silver) to being toxic (such as mercury).
|Dairy products and green leafy vegetables for Calcium|
|Nuts, soy beans, and cocoa for Magnesium|
|Table salt (sodium chloride, the main source), milk and spinach for Sodium|
|Legumes, whole grains, and bananas for Potassium|
|Table salt is its main dietary source for Chlorine|
|Meat, eggs, and legumes for Sulfur|
|Red meat, leafy vegetables for iron|
A large body of research suggests that humans often can benefit from mineral supplementation. Vitamins and minerals are interdependent, requiring the presence of one another for full benefit; taking a multivitamin without minerals is not nearly as effective as taking one with minerals. Extensive university research also demonstrates that the most bioavailable form of supplemental mineral is the chelated mineral (one that is bonded to a specific-size amino acid).
Essential amino acids
An essential amino acid or indispensible amino acid, is an amino acid that cannot be synthesized de novo by the organism (usually referring to humans), and therefore must be supplied in the diet. Nutritional essentiality is characteristic of the species, not the nutrient. Nine amino acids are generally regarded as essential for humans. They are: histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine. In addition, the amino acids arginine, cysteine, glycine and tyrosine are considered conditionally essential, meaning they are not normally required in the diet, but must be supplied exogenously to specific populations that do not synthesize it in adequate amounts. An example would be with the disease Phenylketonuria (PKU). Patients living with PKU must keep their intake of phenylalanine extremely low to prevent mental retardation and other metabolic complications. However, phenylalanine is the precursor for tyrosine synthesis. Without phenylalanine, tyrosine cannot be made and so tyrosine becomes essential in the diet of PKU patients. The following table lists the recommended daily amounts for essential amino acids in humans, together with their standard one-letter abbreviations. (A three-letter abbreviation scheme also exists.)
Recommended daily intake in human Adults mg per Kg body weight for 70Kg human (mg):
|F Phenylalanine 14 (sum with Tyrosine)||980|
|L Leucine 14||980|
|M Methionine 13 (sum with Cysteine)||910|
|K Lysine 12||840|
|I Isoleucine 10||700|
|V Valine 10||700|
|T Threonine 7||490|
|W Tryptophan 3||245|
|H Histidine unknown, 28 in infants (? sum with arginine) (? 1960)|
|R Arginine unknown, required for infants, maybe seniors (?)|
Taurine may be necessary to preserve arterial and collagen pliability at 2 mg/kg/day, small but needed (142mg/day per 70Kg human).
Which amino acids are essential varies from species to species, as different metabolisms are able to synthesize different substances. For instance, taurine (which is not, by strict definition, an amino acid) is essential for cats, but not for dogs. Thus, dog food is not nutritionally sufficient for cats, and taurine is added to commercial cat food, but not to dog food.
The distinction between essential and non-essential amino acids is somewhat unclear, as some amino acids can be produced from others. The sulfur- containing amino acids, methionine and homocysteine, can be converted into each other but neither can be synthesized de novo in humans. Likewise, cysteine can be made from homocysteine but cannot be synthesized on its own. So, for convenience, sulfur-containing amino acids are sometimes considered a single pool of nutritionally-equivalent amino acids. Likewise arginine, ornithine, and citrulline, which are interconvertible by the urea cycle, are considered a single group.
Use of essential amino acids
Foodstuffs that lack essential amino acids are poor sources of protein equivalents, as the body tends to deaminate the amino acids obtained, converting proteins into fats and carbohydrates. Therefore, a balance of essential amino acids is necessary for a high degree of net protein utilization, which is the mass ratio of amino acids converted to proteins to amino acids supplied. All essential amino acids may be obtained from plant sources, and even strict vegetarian diets can provide all dietary requirements, though careful monitoring of nutrient levels is important, as limiting factors become significant when no meat is present in the diet.
The net protein utilization is profoundly affected by the limiting amino acid content (the essential amino acid found in the smallest quantity in the foodstuff), and somewhat affected by salvage of essential amino acids in the body. It is therefore a good idea to mix foodstuffs that have different weaknesses in their essential amino acid distributions. This limits the loss of nitrogen through deamination and increases overall net protein utilization.
An antioxidant is a chemical that reduces the rate of particular oxidation reactions in a specific context, where oxidation reactions are chemical reactions that involve the transfer of electrons from a substance to an oxidizing agent, this generally results in different chemicals to the original ones. Antioxidants are particularly important in the context of organic chemistry and biology. All living organisms maintain a reducing environment inside their cells, all cells contain complex systems of antioxidants to prevent chemical damage to the cells’ components by oxidation. These antioxidants include glutathione and ascorbic acid and are substrates for enzymes such as peroxidases and oxidoreductases. Antioxidants are widely used as ingredients in dietary supplements used for health purposes such as preventing cancer and heart disease. Studies have suggested antioxidant supplements has benefits for health, but several large clinical trials did not demonstrate a definite benefit for the formulations tested, and excess supplementation may even be harmful. Dietary supplementation has few specific antioxidants compared to a broad diet rich in phytonutrients, which will yield thousands of different polyphenol antioxidants available for metabolism.
The term antioxidant (also “antioxygen”) originally referred specifically to a chemical that prevented the consumption of molecular oxygen. In the 19th and early 20th century, antioxidants were the subject of extensive research in industrial processes such as the corrosion of metals, explosives, the vulcanization of rubber, and the knocking of fuels in internal combustion engines.
Early nutrition researchers focused on the use of antioxidants for preventing the oxidation of unsaturated fats, the cause of rancidity. Antioxidant activity could be measured simply by placing the fat in a closed glass container with oxygen and observing the rate of oxygen consumption. However, it was the identification of vitamins A, C, and E as antioxidants that revolutionized the field and led to the realization of the importance of antioxidants in biology.
The possible mechanisms of action of antioxidants were first explored thoroughly by Moreau and Dufraisse (1926), who recognized that a substance with anti-oxidative activity is likely to be one that is itself a target for oxidation. Research into how vitamin E prevents the process of lipid peroxidation led to the current understanding of antioxidants as reducing agents that break oxidative chain reactions, often by scavenging reactive oxygen species before they can cause damage to the cells.
All living organisms contain complex systems of antioxidant enzymes and chemicals, some to combat oxidative damage to cellular components and others to regulate and sustain natural cellular processes such as oxidative phosphorylation and the formation of disulfide bonds.
One major action of antioxidants in cells is to prevent damage due to the action of reactive oxygen species. Reactive oxygen species include hydrogen peroxide (H2O2), hypochlorous acid (HOCl) , and free radicals such as the hydroxyl radical (·OH) and the superoxide anion (O2-). These molecules are unstable and highly reactive, and can damage cells by chemical chain reactions such as lipid peroxidation, or formation of DNA adducts that can lead to oncogenic mutations or cell death if not reversed by DNA repair mechanisms. All cells therefore contain antioxidants that serve to reduce or prevent this damage.
ATP generation and cellular maintenance
Antioxidants are especially important in the mitochondria of eukaryotic cells, since the use of oxygen as part of the process for generating energy produces reactive oxygen species. The process of aerobic metabolism requires oxygen because it serves as the final resting place for electrons generated by the oxidation steps of the citric acid cycle (i.e. oxygen is the final “electron acceptor” of the redox reactions). However, the superoxide anion is produced as a by-product of this reduction of oxygen in the electron transport chain. Specifically, the reduction of coenzyme Q in complex III is a major source of superoxide anion, since a highly reactive free radical is formed as an intermediate (Q·-). This unstable radical can lead to electron “leakage”; instead of moving along the well-controlled reactions of the electron transport chain, the electrons jump directly to molecular oxygen, forming the superoxide anion.
The redox state of the cell’s interior is tightly regulated. The cytoplasm is a reducing environment; however, proteins synthesized for secretion often must be oxidized – particularly to form disulfide bonds between cysteine residues – before export, which normally takes place in the endoplasmic reticulum and Golgi apparatus.
The thioredoxin system contains the 12-kDa protein thioredoxin and its companion thioredoxin reductase. Thioredoxin is present in all sequenced organisms except Tropheryma whipplei (the bacteria that cause Whipple’s disease). The active site of thioredoxin consists of two neighboring cysteines, as part of a highly conserved CXXC motif, that can cycle between an active dithiol form (reduced) and an oxidized disulfide form. In its active state, thioredoxin acts as an efficient reducing agent, scavenging reactive oxygen species and maintaining other proteins in their reduced state. After being oxidized, the active thioredoxin is regenerated by the action of thioredoxin reductase, and thioredoxin reductase is in turn reduced by NADPH.
The glutathione system includes glutathione, glutathione reductase, and glutathione peroxidase. Glutathione peroxidase is an enzyme with four selenium-containing groups that catalyze the breakdown of hydrogen peroxide and protects lipids in cell walls from peroxidation. There are at least four different glutathione peroxidase genes in animals. Glutathione peroxidase 1 is the most aboudant and is a very efficient scavenger of H2O2, while glutathione peroxidase 4 is mainly a scavenger of lipid hydroperoxides. Glutathione is absolutely nescessary for animal life; mice genetically engineered to be deficient in glutathione biosynthesis die before birth. However, glutathione peroxidase 1 is dispensable for life: mice genetically engineered to lack this enzyme have a normal lifespan.
Superoxide dismutase (SOD) is a class of closely related enzymes that catalyse the breakdown of the highly reactive superoxide anion into oxygen and hydrogen peroxide. SOD proteins are present in almost all aerobic cells and in extracellular fluids. Each molecule of superoxide dismutase contains atoms of copper, zinc, manganese or iron. SOD that is formed in the mitochondria contains manganese (MnSOD). This SOD is synthesized in the matrix of the mitochondria. SOD that is formed in the cytoplasm of the cell contains copper and zinc (CuZnSOD). There also exists a third form of SOD in extracellular fluids, termed EC-SOD (also containg Copper and Zinc at the active sites). MnSOD seems to be the most biologically important of these three since mice lacking this gene die soon after birth. Mice lacking CuZnSOD have a shortned lifespan, while EC-SOD lacking mice have minimal defects.
Catalase is a widely occurring enzyme containing four iron atoms in a 500 amino acid protein. Catalase catalyses the conversion of hydrogen peroxide to water and oxygen at rates of up to 6,000,000 molecules per minute. Catalase has a secondary role oxidising toxins including formaldehyde, formic acid and alcohols. The exact role of catalase in animals is still debated since humans with genetic deficiency of catalase (“acatalesemia”) suffer few ill effects and genetic deletion of the catalase in gene in mice is not detrimental either.
Peroxiredoxins catalyze the reduction of hydrogen peroxide, alkyl peroxides, hydroperoxides as well as peroxynitrite. There are presently six different peroxiredoxins known. Genetic ablation of peroxiredoxin 1 or 2 causes shortned lifespan and hemolytic anemia in mice.
Antioxidant applications in nutrition and medicine
Antioxidants are chemicals that reduce oxidative damage to cells and biomolecules. Researchers have found a high correlation between oxidative damage and the occurrence of disease. For example, low density lipoprotein (LDL) oxidation is associated with cardiovascular disease. The process leading to atherogenesis, atherosclerosis, and cardiovascular disease is complex, involving multiple chemical pathways and networks, but the precursor is LDL oxidation by free radicals, resulting in inflammation and formation of plaques.
Research suggests that consumption of antioxidant-rich foods reduces damage to cells and biochemicals from free radicals. This may slow down, prevent, or even reverse certain diseases that result from cellular damage, and perhaps even slow down the natural aging process. This is the basis for the free-radical theory of aging.
Some of the reactions in the body that produce free radicals involve metal ions. Some antioxidants, such as the tannins in walnuts and tea, chelate (wrap around) metal ions. This not only reduces the formation of ion-dependent free radicals, but also prevents the metal ions from oxidizing cells and biochemicals directly.
Some studies suggest that by destroying free radicals and reducing cellular damage, antioxidants in the diet can have positive health effects, such as preventing macular degeneration (studied in the Age-Related Eye Disease Study); maintaining the immune system; potentially preventing neurodegeneration due to oxidative stress; preventing DNA damage; and lowering the risk of cardiovascular disease. Any specific antioxidant may perform only a small fraction of these functions. The mixed results from controlled studies using antioxidant vitamins suggest that other antioxidant substances in fruit and vegetables at least partially explain the better health of those who consume more fruit and vegetables. Dietary antioxidants are not the primary antioxidant inside the body, and there are still many questions as to how polyphenols and other dietary antioxidants protect cells and biochemicals from oxidation. Some antioxidants preserve, or even recycle, other antioxidants such as vitamin E.
Relatively strong reducing acids can have anti-nutritional effects by binding to dietary minerals in the gastrointestinal tract and preventing them from being absorbed. Notable examples are oxalic acid and phytic acid, which are high in plant-based diets. Some tannins also have this negative characteristic. Calcium and iron deficiencies are not uncommon in mideastern diets where there is high consumption of phytic acid present in beans and unleavened whole grain bread. These anti-nutrients can result in deceptively high oxygen radical absorbance capacity (ORAC) ratings given to various “healthy” beverages and foods, particularly:
Foods Reducing acid:
|Cocoa and chocolate, spinach, and berries Oxalic acid|
|Whole grains, maize Phytic acid|
Other extremely powerful nonpolar antioxidants such as eugenol also happen to have toxicity limits that can easily be exceeded with the misuse of essential oils. While antioxidants supplementation is widely hypothesized to prevent the development of cancer, antioxidants may, paradoxically, interfere with cancer treatments. One explanation for this effect is that the growth-promoting environment of cancer cells leads to high levels of redox stress under baseline conditions, and this makes cancer cells more susceptible than normal cells to the further stress of chemotherapy or radiation therapy. So by reducing the redox stress in cancer cells, antioxidant supplements could decrease the effectiveness of the therapy designed to kill them.
Virtually all studies of mammals have concluded that a restricted calorie diet (CR) extends median and maximum lifespan (CR is almost the only protocol to have achieved this). This benefit appears to be at least partly due to substantially reduced oxidative stress. Very large increases in lifespan (up to around 100%) have only been observed in short lived species and the effect in humans is expected to be far less dramatic. The best evidence from animal studies is likely to come from ongoing studies in primates where median life spans have already been shown to be increased and biomarkers of health significantly improved. Due to the long life span of primates, confirmation of maximum lifespan increase will not be available until around 2014. The striking results from animal experiments provide strong evidence that an excess of food reduces life expectancy, although the relationship is not a simple one. Other research suggests that being a little overweight is actually a healthier option in humans (New Scientist 26 November 2005), and a recent major study concluded that mortality rates were positively correlated with waist size, but for a fixed waist size mortality rates were negatively correlated with body mass index (particularly for underweight subjects). As food produces free radicals (oxidants) when metabolized, antioxidant-rich diets are thought to stave off the effects of aging significantly better than diets lacking in antioxidants.
During exercise, oxygen consumption can temporarily increase by a factor of more than 10. This leads to a temporary large increase in the production of oxygen free radicals, resulting in increased cell damage contributing to muscular fatigue during and after exercise. The body uses antioxidants to reduce the amount of such damage. The inflammatory response that occurs after strenuous exercise is also associated with increased occurrence of free radicals, especially during the 24 hours after an exercise session. In this phase too, antioxidants in the body reduce the damage. The immune system response to damage done by exercise peaks 2 to 7 days after exercise, the period during which adaptation resulting in greater fitness is greatest. During this process, free radicals are used by neutrophils in the immune system to identify damaged tissue. As a result, excessive antioxidant levels have the potential to inhibit recovery and adaptation mechanisms.
There is a popular view that those who undertake vigorous exercise can benefit from increased consumption of antioxidants, but an examination of the literature finds support that this is the case only for certain antioxidants at certain levels, and some evidence that very large intake of some antioxidants may be detrimental to recovery from exercise. There is strong evidence that one of the adaptations that result from exercise is a strengthening of the body’s antioxidant defenses, particularly the glutathione system, to deal with the increased oxidative stress. It is possible that this effect may be to some extent protective against diseases which are associated with oxidative stress, which would provide a partial explanation for the lower incidence of major diseases and better health of those who undertake regular exercise.
The antioxidant system that protects lipid membranes from free radicals includes vitamin E, beta-carotene, vitamin A, and coenzyme Q10. The system that scavenges free radicals in the water based cytoplasm includes vitamin C, glutathione peroxidase, superoxide dismutase, and catalase. The effect of each of the exogenous antioxidants needs to be examined separately, although they work in a co-operative manner.
The body of research suggests no benefits from supplementing with vitamin A above normally recommended levels. Recent well-designed studies suggest there are no ergogenic benefits from vitamin E (except for those who do exercise at high altitude) despite its key role in preventing lipid membrane peroxidation. For example, 6 weeks of vitamin E supplementation had no effect on muscle damage indicators in ultramarathon runners. Although selenium is essential to the glutathione antioxidant system which, as mentioned above, is upregulated by exercise, there is no evidence that supplementation with selenium above the RDA is of any ergogenic benefit. However, for vitamin C there is considerable evidence that vitamin C requirements are greater in those who do vigorous exercise, with plasma levels falling with intake of 100mg (well over the accepted RDA) and around 300mg per day being required to maintain blood plasma levels. There is some evidence that supplementation with vitamin C increased the amount of intense exercise that can be done, and lowered the heart rate while doing it (which is indicative of greater efficiency), and that vitamin C supplementation before strenuous exercise reduces the amount of muscle damage. However, some other studies found no such effects, and some research suggests that supplementation with amounts as high as 1000 mg inhibits recovery, although the very short pre-exercise supplementation period in this study may have influenced the results. There is strong evidence that vitamin C supplementation reduces upper respiratory tract infections in ultra-endurance athletes.
In summary, a diet with at least 300 mg of vitamin C is of benefit to those who undertake high intensity or high volume exercise, but it is not clear that normal requirements for vitamin A, vitamin E or selenium are increased.
Although some levels of antioxidant vitamins and minerals in the diet are required for good health, there is considerable doubt as to whether antioxidant supplementation is beneficial, and if so, which and what amount of antioxidant(s) are optimal.
One study of lung cancer patients found that those given beta-carotene supplements had worse prognoses. Two 1994 studies found an increased rate of lung cancer in smokers supplementing with beta carotene. This is believed to be due to antioxidant interference with the body’s normal use of localized free radicals e.g. nitric oxide for cell signaling. Due to the complex nature of the interactions of antioxidants with the body, it is difficult to interpret the results of many experiments. In vitro testing (outside the body) has shown many natural antioxidants, in specific concentration, can halt the growth of or even kill cancerous cells.
In the early 1990s, it was hypothesized that oxidation of LDL cholesterol contributes to heart disease, and several observational studies found that people taking Vitamin E supplements had a lower risk of developing heart disease. Taken together, this led researchers to conduct at least seven large clinical trials testing the effects of antioxidant supplement with Vitamin E, in doses ranging from 50 to 600 mg per day. However, none of these trials found a statistically significant effect of Vitamin E on overall number of deaths or on deaths due to heart disease.
While several trials have investigated supplements with high doses of antioxidants, the “Supplementation en Vitamines et Mineraux Antioxydants” (SU.VI.MAX) study tested the effect of supplementation with doses comparable to those in a healthy diet. Over 12,500 French men and women took either low-dose antioxidants (120 mg of ascorbic acid, 30 mg of vitamin E, 6 mg of beta carotene, 100 ?g of selenium, and 20 mg of zinc) or placebo pills for an average of 7.5 years. The investigators found there was no statistically significant effect of the antioxidants on overall survival, cancer, or heart disease. However, a subgroup analysis showed a 31% reduction in the risk of cancer in men, but not women. The authors interpreted these results as suggesting that “an adequate and well-balanced supplementation of antioxidant nutrients, at doses that might be reached with a healthy diet that includes a high consumption of fruits and vegetables, had protective effects against cancer in men.”
Oxygen radical absorbance capacity (ORAC) has become the current industry standard for assessing antioxidant strength of whole foods, juices and food additives. Other measurement tests include reducing power, free radical scavenging, superoxide anion radical scavenging, hydrogen peroxide scavenging, and metal chelating.
Antioxidants used as food additives to help guard against food deterioration include:
|Ascorbic acid (vitamin C)|
|BHA, BHT, EDTA|
|Acetic acid – found in vinegar; used for pickling|
|Rosmarinic acid – in the form of the herb rosemary and Italian seasoning mixtures in naturally or minimally processed foods, and pet foods|
Antioxidants are found naturally in varying amounts, in vegetables, fruits, grain cereals, legumes, nuts etc. High antioxidant sources include:
|Fruits: blackberries, redcurrants, raspberries and blueberries|
|Vegetables: peppers (chili, red bell) and spinach.|
|Whole grain cereals: barley, millet and maize.|
|Nuts: pecan, pistachio, and almonds|
|Cocoa products: dark chocolate and milk chocolate.|
|Drinks: Coffee (caffeinated and decaffeinated), red wines, and teas (green and black).|
Since the discovery of vitamins, it has been recognized that antioxidants from the diet are essential for healthful lives in humans and many other mammals. More recently, a large body of evidence has accumulated that suggests supplementation of the diet with various kinds of antioxidants can improve health and extend life. Many nutraceutical and health food companies now sell formulations of antioxidants as dietary supplement. These supplements may include specific antioxidant chemicals, like resveratrol (from grape seeds), combinations of antioxidants, like the “ACES” products that contain beta carotene (provitamin A), vitamin C, vitamin E and Selenium, or specialty herbs that are known to contain antioxidants such as green tea and jiaogulan.