The Importance of Clinical Trials for Medical Research and Drug Development

The advancement of medicine in the United States and around the world would be a far cry from what it is today without the use of clinical trials. Testing is perhaps the most important process for medication; it needs to be tested to make sure it’s safe.

There are other reasons in addition to medication testing where clinical trials are useful. They can be conducted to test new or updated equipment, techniques, etc. Medical researchers are interested in the minute details and use clinical trials as a way of gathering information.

Some studies will let just about anyone in perfect health to join. Others require you to have a certain medical condition in order to enroll. This is known as inclusion criteria. There are often several of these eligibility requirements that need to be met before starting.

Additionally, there are often disqualifying conditions known as exclusion criteria. These inclusion and exclusion requirements are put in place for not only to insure integrity of the study, but more importantly to not impose additional or known health risk to the subject.

Women who are pregnant are almost always excluded from clinical trials of drugs for safety reasons. This may even extend to all women of childbearing age or even men who may impregnate a women.

The trial coordinator will make sure you are genuinely eligible before allowing you to enroll. They will also inform you of potential risks and other details specific to the study you are interested in.

Subjects are required to undertake a medical screening to be considered for a medical research trial. Tests vary from trial to trial.

Many clinical trials offer compensation while you are a subject in a research study. This is especially true in Phase I drug trials where the subject is exposed to health risks while not necessarily seeking improvement of a specific condition.

Other trials, usually those regarding specific health problems, don’t pay as much or will only pay a small amount for travel compensation. The reason for this is to make sure that trial seekers are interested in improving whatever problem they have and maintain the integrity of the trial.

Don’t be afraid to ask your the trial coordinator any questions you may have. Also don’t be afraid to express any concern you may have. It’s also a good idea to let your doctors know about any clinical trials you’re thinking about taking part in.

The Role of Essential Fatty Acids in Health and Disease

Since the discovery in 1963 that unsaturated fatty acids are converted to prostaglandins, essential fatty acids (EFAs) have now long been recognized as a factor in the treatment of many health related conditions. Prostaglandins are eicosanoids, which are short-lived, potent, locally acting cellular mediators that produce a broad range of biological affects on a multitude of tissues.

Prostaglandins (PGs) exist in virtually every mammalian tissue, acting as local hormones; they have important physiologic activities. A related series of compounds exist as well, the thromboxanes. Three different fatty acids (FAs) give rise to three groups of eicosanoids characterized by the number of double bonds in the side chains, e.g., PG1, PG2, and PG3. Different groups attach a ring structure in the compound that give rise to series of prostaglandins and thromboxanes, labelled A, B, etc. The leukotrienes and lipoxins are a third group of eicosanoid derivatives.

What is an Essential Fatty Acid?

Essential fatty acids are given that designation not because of the role they have in health but because the human body cannot make them. All fatty acids can be used by the body, but only two are considered essential and both are polyunsaturated fatty acids (PUFA): the omega-6 fatty acid, linoleic acid and the omega-3 fatty acid, alpha linolenic acid. All other fatty acids can theoretically, if all conditions are correct, be made from these 2 oils. EFA’s have been used and researched for the treatment of cardiovascular disease (CVD), brain health and cognition including autism, some autoimmune conditions and cancer. While EFA’s are needed by the body, research has shown some fatty acids are better than others when it comes to therapeutic efficacy.

Fatty acids refer to long chains of hydrocarbons that were once, or can be, a part of the larger molecule known as triacylglyerol (a fat molecule), that normally has 3 fatty acids in it. The naming of omega fatty acids indicates where the first carbon to carbon double bond occurs, for instance, in omega-9 it occurs at the number 9 carbon, in omega-3 it is at the third carbon atom from the methyl end of the molecule. The double bond is what makes the FA unsaturated. Monounsaturated fatty acids (MUFAs) that have one double bond, at the carbon #9, are called omega-9 oils. Olive oil is very high in the omega-9 oil, oleic acid; avocados are as well. Mediterranean diets are high in omega-9 oils, and it has been speculated that these oils in the diet are protective against heart disease based on the lifespan and expectancy of the people of that region. However, as omega-9 oils are not essential, and most diets have more than enough of them, there is no need for additional supplementation.

Omega-6 Fatty Acids and Metabolites

Omega-6 fatty acids are found in plant-based oils, and are considered polyunsaturated fatty acids (PUFAs) because they contain more than one double bond. They are naturally occurring constituents present in sunflower, safflower, corn and soybean oils, walnuts, almonds, sesame seeds, pumpkin seeds and pine nuts. Linoleic acid (LA) is the primary EFA in this group, an 18 carbon long compound. It is prevalent in the standard diet, especially if you eat anything cooked with these oils or eat nuts. LA has little therapeutic value in of itself, but its metabolite, gamma-linoleic acid (GLA) has a stronger effect and is found in certain seeds such as evening primrose, borage and black current. GLA is converted, via an enzyme known as cyclooxygenase, to a prostaglandin of the E series, PGE1. This compound has a direct effect on the reduction of platelet aggregation and contributes to vasodilation, which can benefit those with heart disease. In addition it can also enhance cellular receptors to insulin, which can reduce problems associated with Type II diabetes and insulin resistance syndrome.

Since many people have high amounts of these oils in the diet already through the use of cooking oils, most supplementation is not needed. Our body converts LA to GLA via a desaturase enzyme which makes the molecule longer. This enzyme works as long as it has the proper nutrition and enzyme cofactors: vitamin B3, B6, and the minerals magnesium and zinc.

Arachidonic Acid: How it Creates Disease

However, the natural and more likely chemical conversion of dietary LA will go on to be converted into Arachidonic acid, a 20 carbon long chain fatty acid that is also found in animal products, specifically red meat, dairy and eggs. Arachidonic acid (AA) will lead to PG2 series of chemical mediators, which are pro-inflammatory, contribute to platelet aggregation and increased constriction of the vessels. The platelet aggregation and vessels changes if also coupled with a poor diet- which would favour low nutrients and high blood lipids- can contribute to an increased CVD risk. AA can also create thromboxanes of the 2 series, specifically thromboxane A2 (TXA2) which is a more potent vasoconstrictor and promotes platelet aggregation. In addition, eicosanoid metabolites from AA such as prostaglandin E2 (PGE2), leukotriene B4, 12-hydroxyeicosatetraenoic acid and TXA2 have all been positively linked to carcinogenesis.

The main pathway for AA into PGs is via a cyclooxygenase enzyme pathway, of which (COX) there are at least 2 different enzymes. COX enzymes always give rise to PG or Thromboxanes (TX) compounds. Some medications can block the activity of these enzymes. Several actually target them (commonly known as COX inhibitors). Some examples are Celebrex, Arcoxia and Mobic. These medications are primarily used for their anti-inflammatory nature. Other medications that actively inhibit COX enzymes are NSAIDS such as aspirin, ibuprofen, indomethacin; and some glucocorticoids like dexamethasone. But the COX enzymes are also needed to make other PG of the series 3 class, which are in of themselves anti-inflammatory. Blocking this enzyme with medication eliminates some of the other beneficial effects the PG3s have; anti-inflammatory, anti-thrombotic, anti-spasmodic and anti-cancer. For the temporary benefit of the anti-inflammation that these medications can give, an individual may be putting themselves at risk for cancer and other chronic disease. But other fatty acids such as omega-3s can change that risk.

Omega-3 Fatty Acids: Which is the True Essential Fatty Acid?

Omega-3 fatty acids are more than just plant based oils, they are found in abundance in fish and marine products as well as some in seeds like flax, pumpkin and walnut. These are most commonly deficient fatty acids for people consuming a standard Western diet, which includes not only more red meat products but also a significant amount of processed foods. The EFA of the omega-3 class is alpha linoleinc acid (ALA), similar to LA but with 3 carbon to carbon double bonds. The other FAs of this class that are popular in clinical research are eicoapentaenoic acid (EPA) and docosahexaenoic acid (DHA).

ALA has been touted as the primary EFA for dietary supplementation. Studies using ALA show a positive effect on lipid profiles, and it is beneficial in the treatment of CVD, as well as cancer. However, in humans there are no unique functions of ALA, other than as the precursor for EPA and DHA. In some animals ALA is used primarily in skin and hair.

Flaxseed oil is the most common form of supplementation of ALA. It contains approximately 53% ALA, but also 20% of an omega-9 monounsaturated fatty acid eicosenoic acid (which can also be made from oleic acid), and also 15% of omega 6 fatty acid, linolenic acid, with some of the remaining as saturated fatty acids. High amounts of flaxseed oil in the diet can therefore increase total fat intake considerably. Plus the conversions of ALA to EPA and DHA have been under scrutiny by clinicians and researchers. It is estimated that for every 1 gram of flaxseed oil ingested, only 0.02-6% can be made into EPA and even less, if any, DHA. Given the benefits associated with EPA and DHA, this is not enough for optimal health.

Therapeutic Effects of EPA: Protecting against Heart Disease and Cancer

EPA has the effect of slowing down the production of inflammatory chemicals that result from the arachidonic acid lines. EPA acts as a substrate for the COX enzyme reactions to make anti-inflammatory compounds, and also partially replaces AA in membrane lipids. This replacement allows for more fluidity to the cell.

Specifically, EPA leads to eicosanoids from the series 3 class, PGH3, PGI3 and TXB3. As mentioned above these compounds are anti-inflammatory, anti-thrombotic and anti-spasmodic. In addition, the PG3 class have anti mutagenic nature and discourage tumour cell proliferation. PGE3 from EPA has been shown to be an antagonist to PGE2 from AA in human lung cancer cells. PGE3 also reduces the activity of aromatase, an enzyme that contributes to elevated oestrogen metabolism and has a direct role in oestrogen mediated cancers. EPA, as well as its metabolite which is also present in fish oils- DHA- also reduces the risk of cancer by suppressing free radical reactive nitrogen species, reactive oxygen species, and free radicals which are implicated in tumour progression and also play a role in atherosclerosis.

Therapeutic Effects of DHA: a Key Nutrient in the Central Nervous System

DHA is the most highly unsaturated fatty acid found in cell membranes. It is found in the highest concentration in the membranes of nerve cells, in the retina and plays a key role in brain development. DHA is normally made from EPA when there is enough in the diet- or it is hypothesized that it is made via beta oxidation in cells. Since DHA has 6 carbon to carbon double bonds, it is considered to be ‘superunsaturated’. This allows for even more cell membrane fluidity allowing for more uninhibited reactivity and regulation for cell functions, which is a highly advantageous milieu for the central nervous system and neurotransmitters. DHA is commonly found in a larger compound, phosphatidylserine, in the brain. In this aspect DHA may affect neuronal membranes, cell metabolism, and specific neuro-transmitter systems, including acetylcholine, noradrenaline, serotonin, and dopamine. These compounds can exert significant benefit on cognition, especially those functions which tend to decline with age- including memory, learning, vocabulary skills and concentration. As DHA plays an important role in the development of growing neural tissues, mothers who supplemented during pregnancy had infants that showed higher mental processing scores, psychomotor development and eye-hand coordination at 4 years of age. When given to school children, DHA has shown to play a beneficial role in enhancing learning capacity and academic performance. These factors also point to a role for DHA in autism and other neurological disorders. There is also evidence to suggest that depletion of DHA may be involved in postpartum depression, which is another reason why it should be recommended that all pregnant women, or women who are trying to get pregnant, supplement with DHA.

Is Fish Oil Supplementation then the Answer?

If we follow the rationale that EPA and DHA are not essential because they both can be made from ALA, supplementation or dietary modifications are not necessary for some people: vegetarians who consume ample amounts of nuts and anyone who consume flaxseeds or oil. But it has been noted that the conversion from flaxseed oil makes only a fraction of EPA and perhaps no DHA. The first conversion of ALA to the next FA requires the enzyme delta-6-desaturase that can be affected in many ways. Desaturase enzymes need specific nutrients and enzyme cofactors: vitamin B3, B6, and minerals magnesium and zinc. Low amounts or deficiencies of those nutrients inactivate the enzyme. An elevated alcohol intake, trans-fatty acids, and saturated fats can all inhibit delta-6-desaturase. Also responsible for lowered enzymatic activity are the viruses HIV and Epstein-Barr virus (EBV), of which EBV causes infectious mononucleosis and has been implicated in patients with Chronic Fatigue Syndrome. Excess insulin, a factor in Type II Diabetes and Insulin Resistance Syndrome can also inhibit the enzyme pathway. A higher intake of omega 6- oils also inhibits the conversion of ALA to EPA by competing for the same delta- 6-desaturase.

Theoretically, humans evolved on a diet consisting of a 1:1 ratio of omega-6 to omega-3 fatty acids. Currently, the typical Western diet consists of omega-6: omega-3 ratios between 10:1 and 25:1 and in some cases may be as high as 40:1. Since omega-3 and omega-6 FAs compete for the same enzyme, the high amounts of omega-6 FAs lead to elevated levels of AA in cell membranes. This imbalanced fatty acid ratio is one of the major underlying factors in chronic inflammatory health problems. The metabolites of AA can contribute to CVD and cancer, the two main killer diseases of our age. By manipulating the levels of AA, we can change our disease risk and over all decrease mortality. The best way to change dietary FA is by the addition of fish oils into the diet. It is important to consider the quality and cleanliness of the fish or fish oils consumed, in particular the mercury which is polluting the oceans and the fish. Also of importance are newer dangerous man-made chemicals like dioxins and polychlorinated biphenyls (PCBs) that also make it way into the fish bodies via the sea. By supplementing with clean, high quality fish oil we can increase health and wellness, clear thinking and awareness, not only for ourselves but for our children and future generations.

Health and Medical Grants

“Health is wealth”, it is said. It is true. However, so many Americans do not care about visiting a doctor for regular checkups or even in times of trouble, just because they are unable to bear the cost of the examination. American healthcare is a hotly debated topic in the political realms as seen in the recent past of the nation’s movement. The future of the nation’s healthcare is one that is under screening. There are some who have private health insurance and they have no reason to fear unlike the millions of Americans without any coverage. For the latter crowd, government health grants can be lifesavers.

What issues are medical grants available for? Medical grants are available for nearly every type of medical condition. If you or someone in your family is struggling to pay for hospital bills, eyeglasses, health appliances, hearing aids, or prosthesis, medical grants are recommended. It could be the cost for specialized treatment that is unaffordable. This could include any therapeutic help such as therapy for drug and alcohol abuse, stroke, heart disease, cancer, Parkinson’s disease or Alzheimer’s. These grants will cover various expenses such as medicines, surgeries, fertility treatment, etc.

Medical grants that cover specific medical costs are great, but what about those Americans who need extensive healthcare that onetime health grants cannot cover? There are assistance services that subsidize the cost of health insurance and provide accessible insurance to families with low income. There are two government medical grants programs – Medicaid and Medicare. These programs ensure that all Americans, including children, have health coverage.

There are a number of medical grants available. You have childcare financial assistance, employment support programs, cash disability benefits, health care financing grant, medical research grants and scholarships, children health insurance grant, Medicare grant programs, disability insurance programs, and medical bills payment assistance programs. With the help of these grants, those suffering from some kind of disability but who wish to return to their workplace can do so without suffering any loss in health benefits. There are various employment support programs that provide Health Grants. This helps the transition process and you will not miss any of the disability grant income that you so got used to having.

Grapefruit and Medication Interactions

Many people may not be aware of it, but the consequences of certain drug interactions with grapefruit juice can be life-threatening, if not fatal. Affecting the effectiveness of many types of medications, grapefruit side-effects can range from low energy to kidney failure.

It has been observed that it does not take much grapefruit juice to alter the benefits of certain medications. A 47% decrease in the effectiveness of medications from grapefruit juice can be seen after consuming just one glass. Additionally, it can take more than 24 hours for the effects of a single glass to wear off. This is why people who drink one or more glasses of grapefruit juice daily and take certain medications have become seriously ill.

So what exactly is it about grapefruit juice that causes such serious side-effects. Studies have shown that grapefruit inhibits a crucial enzyme, sometimes with fatal results. It has been noted that the same enzyme in the liver that is responsible for breaking down drugs also is responsible for metabolizing grapefruit into useful components. When there is an interference with drugs and grapefruit juice, it is often a scenario where the presence of grapefruit juice overloads the system thereby preventing the drugs from being broken down properly and dispersed throughout the system. The following offers a brief overview of drugs that may be compromised by the presence of grapefruit: Depression, cholesterol, cancer, impotence, pain, and high blood pressure.

Researchers who have been studying this phenomenon have seen cases of grapefruit juice interactions occurring in a wide demographic range. Two of the most susceptible groups however include snowbirds and those who are beginning diets to lose weight. Most northerners who pack-up and head south for the winter are usually unaware of this condition, and learn the hard way resulting in trips to the emergency room. Similarly, many people who want quick weight loss often try crazy diets that usually include drinking a large quantity of grapefruit juice. While their intentions are to lose weight, they are often faced with more serious health problems. These weight loss issues could be prevented by seeking online herbal remedies advice.

In closing, remember to discuss all medications and dietary patterns with your doctor. Being honest and open can save your life.