Pharmaceutical drugs are chemicals that are designed to prevent, diagnose, treat or cure a disorder. In laymen terms, we simply call them medicines. Pharmaceutical products commonly known as medicines or drugs are a fundamental component of both modern and traditional medicine. It is essential that such products are safe, effective and of good quality, they are prescribed and used rationally.
Drug therapy (Pharmacotherapy) is an important part of the medical field and relies on the science of pharmacology for continual advancement and on pharmacy for appropriate management. Like any other branch of science especially medical science, pharmacotherapy is dynamic and constantly evolving, this has brought the idea of nutraceuticals as a major branch of pharmacotherapy.
Dr. Stephen De Felice first coins the term nutraceutics in 1989 and he defined nutraceuticals as “food or parts of food that provide medical or health benefits including the prevention and treatment of diseases”. The term functional food is also used to refer nutraceuticals. In the states of Canada and Great Britain, a functional food is essentially a food, but a nutraceutic is an isolated form or concentrated form. This means most nutraceutics have been isolated, purified and formulated into several dosage forms.
Nutraceuticals have emerged not only as a necessity but also as an alternative for prevention and treatment for various chronic diseases. This field is getting diversified towards natural nutraceutical ingredients and it is believed that product and ingredient innovation are the way forward for the nutraceutical industry. There is also a trend to incorporate traditional herbal ingredients (usually Ayurvedic) into the nutraceutical portfolio. The major difference emerging between pharmaceuticals and nutraceuticals is with respect to varied regulatory status in different countries. Considering the impact of different systems of ancient medicine worldwide, the trend for the nutraceuticals is no different than what the world has witnessed for the pharmaceutical industry. With the increase in new clinical applications, nutraceuticals are likely to fall within the novel foods and ingredients regulations but their purity, dosage requirements and clinical consequences exceed those of most health foods. The future of nutraceutical industry and its role as biomedicines in the disease management will be governed by control of purity, safety and efficacy without inhibiting innovation. The application of pharmaceutical standards, standardization of formulations, dosage forms and production controls are likely to be a challenge and that can either make a boom or could paralyze the industry.
Interactions between foods/dietary supplements and drugs present complex and challenging problems. They may arise either from alteration of the absorption, distribution, biotransformation, or excretion of one drug by a food/dietary supplement or from a combination of their actions or effects. The interactions can have a marked influence on the success of drug treatment and on the adverse effect or side effect profiles of many drugs; however, the interactions are not always harmful to therapy, but in some cases they can be used to improve drug absorption or to minimize adverse effect. Most food/dietary supplements and drug interactions occur through one of three mechanisms:
Induction of Drug Metabolism
Induction or inhibition of enzymes in the gut by nutrients may lead to a significant change in oral bioavailability of drugs or vice versa. Enzyme induction effect is the ability of numerous foods or drugs to stimulate the production of drug-metabolizing enzymes in the liver, which may result in increased metabolism of the administered drug as well as other related or even unrelated drugs. The activity of the drug-metabolizing enzymes in liver microsomes, as well as the structure and amount of ER and even the size of the liver, are influenced to a great extent by the administration of drugs and hormones, and by age, sex, temperature, nutritional status, and psychological and pathological states of the subject. Enzyme induction involves an adaptive increase in the number of molecules of a specific enzyme in response to an enzyme-inducing agent. Inducers of drug oxidation have several features in common, such as lipophilicity, the ability to bind to CYP450 enzymes, and relatively long biological half-lives. Many drugs share these properties without inducing enzyme synthesis. When drugs metabolized in the GIT after entering the gut, they are exposed to a number of systems with the potential to chemically modify or to chelate the drug molecules that are not found within the tissues of the host. These include extremes of pH, unabsorbed nutrients and xenobiotics, digestive enzymes, and intestinal microflora. The intestinal microorganisms represent a potent, diverse, and adaptable metabolizing force that has large potential for the metabolism of drugs and environmental nutrients. The gut flora consists of a complex, dynamic mixture of aerobic organisms that may show large variations (Enterobacteria, Lactobacilli, enterococci, Bacteroides, Clostridia, and Bifidobacteria). This gut flora may be altered by changes in the diet, by diseases, and by the administration of foreign compounds. The gut microorganisms thus represent an adaptable changing source of metabolic activity that may show large interindividual and intraindividual variations in the numbers and types of organisms present. In addition, intestinal transit time and defecation frequency may affect the duration of exposure of a drug to the gut flora in vivo and produce pronounced temporal variations in levels of metabolites.
Inhibition of Drug Metabolism
Variously termed Kcat inhibitors, suicide enzyme inactivators, enzyme-activated irreversible inhibitors, and suicide enzyme inhibitors represent a relatively new approach to specific irreversible inactivation of enzymes. Simply stated, this approach requires the inhibitor to contain a latent reactive grouping and to be accepted as a substrate by the target enzyme, following which the normal catalytic activity of the enzyme results in its own
irreversible inactivation or “suicide.” A number of food–drug reactions are based on the inhibition of metabolism of certain drugs by food; the result of such interactions is an increase in the duration and intensity of pharmacological activity. Two points of view are seen regarding the clinical value of enzyme inhibitors:
Nutraceuticals are naturally fortified foods which contain essential nutrients and are taken to supply the body with nutrients to replace lost nutrients or freshly supply the nutrients.
Fortified foods are also recommended in cases of chewing difficulty. In an intermediate stage of obstruction (e.g., insufficient swallowing), an enteral formula is necessary in the diet to provide the proper nutritional requirements. Foods are most often fortified with multivalent cationic minerals, such as calcium, iron, magnesium, aluminum, and vitamins, like C, D, E, and B-complex. Although it is clear that certain drugs should not be taken with antacids, multivitamins, and mineral supplements, many do not consider the implications of taking their daily medications with the general food we take. Currently, the
Food and Drug Administration (FDA) standardized meal used in product labeling of drug–food interactions is a high-fat, high-caloric diet that provides only a small amount of dietary vitamins and minerals (FDA, 2007). High-fat meals may increase the amount of theophylline in the body, whereas high-carbohydrate meals may decrease it. It is important to check which form the patient is taking because food can have different effects depending on the dose form (e.g., regular release, sustained release, or sprinkles). Food increases the absorption of theophylline, which can result in side effects of nausea, vomiting, headache, and irritability. As a result, many drugs are labeled may be taken with or without food while they may be also labeled do not take with antacids. The biochemical mechanisms that cause drug antacid interactions are the same mechanisms that cause drug interactions with fortified foods. Chelation and adsorption interactions, which cause decreased drug absorption, will certainly occur between fortified foods and drugs. However, due to the fact that some fortified foods contain a quantity of polyvalent ions that approaches or exceeds that contained in antacid formulations, changes in gastric pH, changes in urinary pH, and otherwise unspecified decreases in absorption are also possible. The implications of these interactions can range from clinically insignificant to severe. There are several mechanisms by which minerals interact with drugs. When described in the literature, they are often listed as drug–antacid interactions. However, as emphasized here, it is important to consider the nutrient content of foods, especially those that have been fortified with minerals, as containing sufficient quantities of minerals to be equivalent to antacids with interaction capability. Chelation, adsorption, changes in gastric pH, changes in urinary pH with resultant changes in renal clearance (CLR), and uncharacterized decreases in absorption are the five causes of moderate to major drug–mineral interactions described in the literature. Foods containing significant quantities of multiple minerals could cause moderate or major interactions, although each mineral individually may cause only a minor interaction.
Chelation is the formation of a complex involving a metal ion and two or more polar groupings of a single molecule. The overwhelming majority of the drugs affected by chelation with multivalent ions are antibiotics and highly reactive nutrients e.g. Vitamins, particularly the quinolones, tetracyclines, antioxidants and some oral cephalosporin.
Specific examples of common supplements affecting pharmaceuticals are listed below, supplements containing any of the following are usually given special consideration.
1. Gingko Biloba containing supplements:
The seeds and fruits of Ginkgo biloba have been part of traditional Chinese medicine (TCM), particularly for the treatment of asthma, indigestion, cough, and chilblains (i.e., pedal edema related to cold exposure). In vitro animal and clinical studies on the effect of ginkgo extracts on platelet aggregation, coagulation, and various CYP450 isoenzymes are conflicting. The concurrent use of ginkgo with antiplatelet, anticoagulant, or antithrombotic agents increases the risk of bleeding. Hyphema, subphrenic hematoma, and intracranial hemorrhage have been reported.
2. Garlic containing supplements:
Garlic has been mentioned in medicinal texts since the Ebers papyrus (c. 1550 BC). Garlic extracts are commonly used by HIV-infected patients, because these extracts possess antiseptic, bacteriostatic, antiviral, immune-enhancing hypotensive, and antihelmintic properties. Traditionally, garlic has been used to treat respiratory catarrh, recurrent colds, bronchitic asthma, influenza, and chronic bronchitis. Currently, garlic and garlic preparations are investigated for their antihypertensive, antiatherogenic, antithrombotic, antimicrobial, fibrinolytic, cancer preventive, and lipid-lowering effects and have been used for preventing cardiovascular disease. The active component ajoene in garlic inhibits collagen-induced platelet aggregation, and garlic is used for its antiplatelet and fibrinolytic effects in patients with cardiovascular disease. However, the risk of bleeding in people using anticoagulant or antiplatelet agent increases, so its concomitant use should be avoided. The use of large amounts of garlic can cause platelet disorders and/or hemorrhage. Garlic supplements should be discontinued approximately 10 days before elective surgical procedures, especially by patients using aspirin or warfarin. The use of dried garlic powder causes some modest short-term reduction (8–12 weeks) in total cholesterol concentrations, but these effects are not sustained over 6 months. In the presence of garlic supplements, blood concentrations of saquinavir decreased by approximately 50% among our study participants. Garlic contains a large number of biologically active constituents.
3. Panax Ginseng containing Supplements:
Ginseng refers to the root of Panax species. The most commonly examined species are Panax ginseng (Asianginseng), Panax quinquefolius (American ginseng), and Panax japonicus (Japanese ginseng). Ginseng is advertised as an immune system stimulant that increases vigor, sexual potency, well-being, and longevity, and for use as an antihyperglycemic agent. Ginseng has both hypertensive and hypotensive effects, with the latter caused by the enhanced synthesis of nitric oxide (NO). In Chinese medicine, ginseng is used for myocardial infarction, congestive heart failure, and angina pectoris; however, current evidence does not support its use for cardiovascular conditions.
4. Saw Palmetto containing supplements:
The extracts of saw palmetto have been used for treatment of abdominal disorders and dysentery, whereas the fruit of the plant is a food and nutrient. The crude extracts have been used for centuries to improve breast size, sperm production, and sexual vigor. Currently, saw palmetto is one of the top five most popular herbal products to treat the symptoms related to benign prostatic hypertrophy; it is also a diuretic and urinary antiseptic. When saw palmetto is used for BPH, the prothrombin time (PT) and activated partial thromboplastin time (aPTT) were normal, but the bleeding time was prolonged to 21min (normal: 2–10 min).
After cessation of saw palmetto, the bleeding time returned to normal values within 5 days. Saw palmetto inhibits cyclooxygenase and increases bleeding with warfarin (Bressler, 2005). In addition, its unsupervised use can result in cholestatic hepatitis, acute pancreatitis, and intraoperative floppy iris syndrome during cataract removal because of loss of iris tone.
5. Grapefruit Juice containing supplements:
The interaction between grapefruit juice and a variety of drugs has been widely reported. It appears that one or more flavonoids found in grapefruit juice inhibit CYP enzymes. This results in reduced metabolism of drugs that are cleared by the same system; drug bioavailability can markedly augment by as much as 200%. Patients should avoid drinking grapefruit juice for 2h before and 4h after taking drugs in this category. Drugs with large volume of distribution are in this category and a good example is the Statins. If the drug is in an extended release dosage form, patients should wait until 6h have passed before drinking grapefruit juice. The resulting increase in drug levels can lead to an increase in therapeutic effect, adverse effects, and/or toxicity. The fruit has been proven to be a good source of vitamins C and the B complexes, as well as calcium, potassium, and magnesium.
6. Mono Amine Oxidase (MAO) Inhibitors
Worthy of mentioning is the Mono-Amine Oxidase inhibitors. Perhaps the most feared food-drug interaction is between MAO inhibitors and the amino acid tyramine, which is found in a variety of aged, fermented, overly ripe, or pickled foods and beverages and, to a lesser extent, chocolate and yeast-containing foods. Examination of various foods and drinks has shown that many are rich in tyramine content, for example, certain cheeses, Chianti wine, some beers, yeast products, and schmaltz pickled herring, whereas others, notably citrus fruits and caffeine-containing drinks, may cause bizarre effects in patients on MAO inhibitors therapy due to their dopamine, tyramine, or serotonin (5-hydroxytryptamine) content. There was an effect on individuals consuming cheese or other foodstuffs high in tyramine content while using MAO inhibitors; the result was that without the detoxifying activity of MAO, the ingested tyramine entered the bloodstream and resulted in a potentially fatal hypertensive crisis. Because more than 10mg of tyramine seems to be required to produce significant hypertension, the most dangerous foods are aged cheeses and yeast products used as food supplements. Tyramine is indirectly sympathomimetic and is a pressor amine or substance capable of liberating stored catecholamines. When its metabolism is suppressed, as it is by MAO inhibitors, it can cause a significant release of norepinephrine, resulting in markedly increased blood pressure, cardiac arrhythmias, hyperthermia, and cerebral hemorrhage. The occurrence of these hypertensive side effects (forceful, heartbeat, severe headache, and hypertension) depends on the duration and intensity of action of the MAO inhibitor antidepressants, the variation in tyramine content in the diet, and the marked individual variation in responsiveness of the patient.
.Sean: a dedicated health professional with more than 20 years of health and nutrition education, industry background, and personal experiences. Sean’s journey began at National Holistic Institute where he studied health and nutrition and he later became a certified trainer and weight loss specialist with the National Academy of Sports Medicine. Though his education has positioned Sean as an expert in the health and nutrition industry, it is his own diagnosis of heart disease that has enabled Sean to open up and assist others with their own unique health and nutrition needs.