Wednesday, January 30, 2008

Physician Heal Thyself

As a pharmacist I walk a thin line. Morally I feel obligated to offer information to patients about alternative therapies when appropriate. At the same time I feel I hold back for fear of being reprimanded by the board of pharmacy or admonished by disgruntled physicians who may not appreciate my suggestions. "First do no harm", has at times become; first protect yourself legally; and that's unfortunate.We have been forced to practice defensive medicine. Our medical system, as technologically advanced as it is, is in disarray. Thousands of MRI's, CAT scans, X-rays, blood work are being performed every day; many needlessly. Prescriptions are being handed out like candy; at times just to pacify the patient. Unfortunately these patients soon realize just how expensive the piece of paper they hold in their hands really is.

At the pharmacy I'm approached by patients all the time with various questions. In an attempt to more effectively provide them with helpful information, I usually ask brief questions about their conditions and if they had discussed their concerns with their physicians. Often time the answer is no. Excuses may range from, "I could see that he was busy, so I didn't want to bother him" or "We did discuss it, but I'm not sure I understand" or "I'm concerned about any side effects or drug interactions" or "Isn't there anything else I could take that's over the counter" or "This is too expensive, I can't afford it". In addition, many patients are seeing several doctors and often times each doctor is unaware of what the others are prescribing. In an attempt to save money the patient frequents several pharmacies in order to get the best price. All of this leads to a disorganized medical system which leaves the patient in a vulnerable position as well as their health care providers. If Dr. X isn't aware that Mrs. Smith is taking diazepam, he may write for another sedative, alprazolam. If her primary care physician prescribed the diazepam for muscle spasms and her psychiatrist prescribed alprazolam for anxiety, the patient may believe that these two drugs have nothing in common and it doesn't even occur to her to mention it to either doctor.

Time and again I see that physicians are not aware of their patient's complete drug history and even less aware of what they take over the counter. It is our responsibility as pharmacists to bring this to the doctor's awareness, but we are hindered by not having access to the patient's complete medical history, which includes other pharmacies that they go to. In these cases it seems obvious that the person most capable of resolving these issues is the patient herself, by being forthcoming with the information. I'm all for patient responsibility, but what do you do with an elderly population that has a difficult time remembering and understanding medical jargon?And what of individuals whose English is their second language and have difficulty understanding as well? By no means are these the only patients that we have to be concerned with. The population at large still sees the physician as a patriarchal figure, an expert when it comes to their health. They mistakenly assume that practitioners have an ongoing dialogue amongst each other, in which they routinely partake in conversations regarding their patients. This naive understanding of the medical system, contributes to a patient's vulnerability and less than optimal medical care. I am a strong supporter of patient responsibility--to a certain extent. They are responsible for communicating openly with all their health care practitioners and asking questions, until they are satisfied that they understand all options regarding therapy they are receiving.

However how is it possible for someone outside the medical field, to understand completely what is best for them? It seems that every nightly news show is full of contradictory research conclusions. Part of the problem is sensational headlines, whose only purpose it to captivate the audience's attention. Viewers are left with the misleading headline in their minds and aren't aware of the details in the research, which offers a more comprehensive analysis. Of course we are taking for granted that the study itself was well designed and accurate. Patients are bombarded with contradicting information on a regular basis. Even if they want to take an active role in their healing process, they are overwhelmed with questions that seem to have no end. To make matters worse, according to Dr. John Abramson of Harvard Medical School, many popular studies that have been done in the recent past have had significant flaws at best and outright fraudulent at worst. How are patients to know the difference if practitioners themselves have a hard time deciphering the good ones from the bad?

What I once thought to be research that was done impeccably, with the highest scientific standards, published in trustworthy peer reviewed journals, is no longer true. I went to college in the eighties, a time in which I was made to believe that scientific research was almost sacred in nature. Scientists were seen as objective individuals who would above all else do everything within their power to avoid any bias toward a particular outcome. Dr. Abramson explains in his book Overdosed America that we are standing on shaky ground. Research that once was done by nonprofit organizations, such as universities and hospitals, is now being done by drug companies. Our regulatory agencies which once were forbidden to take money from drug companies are now being subsidies by them. The journals that once had my full confidence, are now receiving millions of dollars from drug companies in exchange for advertisements. Physician's prescribing habits are not only being monitored by insurance companies but also by drug companies and their sales people, in order to more efficiently target marketing. In addition, practicing physicians have routinely been recruited to participate in clinical studies. They were modestly reimbursed for their time if at all; now participating in clinical research means big dollars. Not only are the drug companies doing their own research, but they are hiring their own doctors to do the follow-up clinical studies. This does not mean that all results are unreliable, but one has to question the validity of studies financed through private companies. Where are the safeguards against bias?

Practitioners that are hesitant to recommend or merely tolerate the idea of alternative medicine should consider the issues that have arisen over the last few decades within our own medical system. Healthy skepticism is necessary when evaluating any therapy now more than ever before. Fortunately many physicians have the capacity and aptitude to thoroughly evaluate a study. Statistical analysis is now taught at most medical schools. Unfortunately, evaluating alternative therapies is a bit more complex, only because their knowledge base in these therapies is minimal. Most medical schools don't have these courses available.There are some medical school curriculums which offer courses on alternative and complimentary approaches. These are few and are most often offered as electives within the required curriculum. Some schools are on the cutting edge of training their physicians in a more comprehensive fashion. Often these opportunities are available to medical school graduates when they finish their standard training. These already established physicians chose to do a fellowship in integrative medicine. One such school is the University of Arizona Integrative Medicine Program. This program was founded by Dr. Andrew Weil a foremost expert in the field. In an attempt to educate the practitioner at large, the program also offers continuing education courses on various therapies in complimentary and alternative medicine (CAM). Educational institutions such as this one are at the forefront of a changing paradigm in medicine. They are doing much to dispel the negative stereotype that CAM approaches have received over the last forty years or so. They have taken a hard look at CAM therapies and identified those that are efficacious and beneficial.

Although the number of clinical trials being conducted on CAM therapies are growing in number, there is an undercurrent of disapproval in order to show that most of these therapies are ineffective at best and harmful at worst. It is logical that given the number of therapies available to the consumer, some will be shown not to work and some may prove to be unsafe, but the amount of negative reports in the media suggest a negative bias. There was a news report a few years ago whose headline read "Study proves that St. John's Wort is no better than placebo". In that same study they also compared the efficacy of a popular antidepressant medication. What the media didn't convey was that this antidepressant, which was widely used, was shown to be less effective than placebo. What would it mean to the drug companies if an herb was found to be effective in mild depression? Millions of dollars would be lost.It is difficult to discern credible reporting from what amounts to be agenda driven advertisement.

It is essential that we understand the obstacles that we are faced with and take it upon ourselves to unscrupulously assess the reliability and credibility of the report, whether it be conventional or alternative. We need the support and guidance of respected institutions to help us lead the way to a more holistic model of medicine. At the same time we need comprehensive resources to be easily accessible. Having these support systems in place would not only afford us the ability of providing quality care, but would simultaneously reduce our exposure to liability. According to the University of Arizona Program in Integrative Medicine (PIM), the legal issues that health care providers face when recommending or discussing complementary and alternative medicine modalities in their office are as follows:

Malpractice liability for inadequate informed consent

Licensure and credentialing

Scope of practice (the legally authorized practice boundaries for providers)

Professional discipline (discipline for professional misconduct)

These concerns are valid and one can understand the hesitancy that many practitioners have. From their perspective they would be jumping in a fire hoping to avoid getting burned. In the midst of these obstacles there are seeds of hope. We as patients and as healthcare providers must not capitulate to this challenge. We must avoid complacency and strive for a healthcare environment that is open to new thought and offers more options. PIM offers suggestions and guidelines to follow which will help in traversing these murky waters. When a patient asks about alternative therapies the following should be considered:

What is the curability rate with conventional care?

Weigh quality of evidence, invasiveness, and toxicities of each therapy.
Patient clearly understands the risks and benefits of each option and accepts those risks.It is also important to familiarize yourself with organizations that have been established, in order to demystify CAM therapies. The Consortium of Academic Health Centers for Integrative Medicine (CAHCIM) is an organization responsible for performing rigorous studies on various medical therapies in order to create new models of clinical care, these models would integrate biomedicine, the complexity of human beings, the innate nature of healing, with the diversity of therapeutic systems from all over the world. It understands that the western medical model, although superb at treating many diseases and conditions, also has limitations. At the same time it acknowledges that for millennia there have been effective medical models from around the world. Some of the academic medical centers that are members of CAHCIM include: University of Arizona, Harvard, Georgetown, Duke, and Columbia University to name a few. The following is a list of resources that are also a good place to start:

American Botanical Council

American Herbal Pharmacopoeia

Consumer Labs: Randomly test dietary supplements and release their finding to the public Extensive website with information pertaining to both conventional and CAM treatments.

FDA Food Manufacturing Practices (GMP): Sporadically monitors products off the shelf

Independent Drug Information Service (iDiS)

National Center for Complimentary and Alternative Medicine (NCCAM)

National Institute of Health

National Sanitation Foundation (NSF): Dietary supplement quality verification, they use GMP
compliance standards

Overdosed America, Dr. John Abramson

Powerful Medicines, Dr. Jeffrey Avron

The Association of Official Analytical Chemists (AOAC)

The Compendium of Asian Patent Medicines

University of Arizona Integrative Medicine Program

United States Pharmacopoeia (USP): Dietary supplement quality verification they use GMP compliance standards

World Health OrganizationGiven the available resources and I'm sure there will be more to come, a practitioner who has a sincere interest in offering his patients more options, can feel more comfortable with the use of alternative medicine. It saddens me to think how the western medical community has so often disparaged and looked upon other medical models with disdain and total disregard. We don't have all the answers, far from it. All medical traditions have blind spots, strengths and weaknesses. Western medicine would benefit from a visit to the therapist, there it would hopefully have a revelation, and it would realize that it is not omnipotent. Could it be projecting onto other medical models what it is afraid to accept of itself? We bare and share the same responsibility, which is to provide the best medical care available to our patients.

Monday, January 28, 2008

Are Supplements and Vitamins Necessary?

The word vitamin comes from the Latin words, vital (life) and amine (building blocks of DNA). Most vitamins we take in from dietary sources. In an ideal situation (when we're young, disease free, healthy diet), our body receives and manufactures all the essential vitamins and minerals that it requires for maintaining physical, emotional and mental health. However, for various reasons vitamin deficiency has been a significant problem, mostly due to poor diet. Although agricultural practices have increased the world's food capacity, there are still to this day many areas of the world in which food is not readily available. Thus, these societies do not receive important nutrients simply due to starvation. In addition to present day famines , western cultures have developed unhealthy lifestyles, specifically with respect to diet and exercise.

The fact that we are becoming obese and live sedentary lifestyles is not earth shattering news. What has not been emphasized enough however, is that while we are taking in more calories, they are not necessarily healthy ones; in fact the opposite seems to be true. Less than a century ago, we were more active. Having to walk to where ever it was we had to go, exposed us to the outdoors, which in turn increased our bodies ability to produce its own vitamin D; a vitamin that research is looking more and more into and finding benefits for use in various diseases. The point is this: yes it's true that if (and in this day and age, it's a big if), you are a healthy person, with a healthy lifestyle, most likely you don't require supplements of any kind. But if you fall into the group of people, who have not been able to maintain a healthy diet regimen due to long hours at work, busy schedule at home and overall lack of knowledge on what it constitutes to eat healthy, then more than likely you could benefit from some supplements added to your diet.

Which supplements to consider, will be age specific and also dependent on your physical, emotional, and mental condition. Are you looking for supplementing overall health? Or do you have specific illnesses and symptoms you want to target? Supplement selection should be carefully researched on an individual basis and discussed with your physician or health practitioner. What I see most often in the pharmacy are clients who come to the counter and ask about a particular supplement in which someone they know has recommended. There is nothing wrong with listening to suggestions as long as you do the follow up which is to ask if that particular supplement would be of benefit to you. Supplements can be expensive, especially if your personal physical condition warrants that you take more than one, so it becomes imperative from a health stand point but also a financial stand point that you take the time to educate yourself thoroughly about which supplements would be of most benefit to you.

There are many places to educate yourself. The internet is a great source if you know where to look. You can ask your doctor or a pharmacist. A pharmacist who specializes in Integrative Medicine would be especially appropriate. They can guide you through what can be at times an overwhelming plethora of information. This is a fairly new field of medicine, but an invaluable one. The role of an Integrative Pharmacist is to evaluate your circumstances and educate you as to what options you might have or would be most appropriate for your condition and your financial situation. It may be as simple as making you aware of less expensive alternatives. For example, I have had several clients who have been switched from antidepressant to antidepressant, it isn't unusual for someone to be on two at a time, only to be switched yet again to a more expensive drug new to the market. In frustration, they tell me they can't afford the medication and that as soon as the doctor finishes handing out his samples, they will have to stop taking it. I explain that very often patients who don’t respond well to antidepressants, especially if they have already tried several, might have low levels of folate or folic acid. More often than not folic acid supplementation along with vitamin B6 (pyrodoxine) and vitamin B12 (cyanocobalamin) significantly improves their response to a less expensive generic drug. This is merely one example of how supplements, in this case vitamins, can make a significant impact on therapy response and effectiveness.

Contemporary medicine is more and more complex. Physicians are finding it necessary to specialize more and more, being able to keep up with the most recent research, and understanding in depth what therapy will be most effective for each individual can be an overwhelming if not impossible task. The benefit of this specialized approach to medicine would seem to be obvious. A physician is able to be an expert in his field. But this has also created a problem in our medical system. So many medical students today are specializing, that we are losing the glue that holds it all together. This glue that I'm referring to, which is essential to practicing good medicine, is our front line doctors and practitioners. The family physicians and pediatricians for example, who are responsible for practicing preventive medicine (educating the patient on staying healthy), identifying and treating diseases when they arise, but they are also the ones responsible for collecting all the data and reports that are being produced by the specialists that their patients have been referred to. If this seems like a mouthful, it's more than that, it's more than a handful. Because of the increase in rate of physicians who become specialists, there are less and less front line physicians. The ones that remain are overworked and at times overwhelmed.

There is a medical crisis in this country for various reasons, but substandard communication between health professionals and their patients is of major concern, in part because there is so much information to keep track of. We need an integrative approach to medicine. Dr. Andrew Weil is a physician who has developed an Integrative Medicine program at the University of Arizona Medical School and there are other universities across the country that have begun to incorporate this idea into their medical schools. The basic philosophy is this: you treat the body as a whole and you treat the patient with a team of physicians that work closely together. Their clinic works with family practitioners, specialists, as well as alternative practitioners; acupuncturists, massage therapists, physical therapists, psychotherapists, pharmacists, nutritionists, etc. Although integrative medicine is becoming prevalent, it is by no means a part of mainstream medicine.

In the meantime, patients need to do the best with what they have available to them. Towards that goal is familiarizing yourself with what types of therapies are available and being able to decide which ones are credible and which ones aren't and that most certainly includes supplements. Knowledge is power. It is not enough to explain the benefits and risks of taking supplements. We are people first and patients second and we are responsible for our own health. In order to make informed decisions we need to understand why vitamins are necessary or "essential" to good health and how they work. The words essential and non-essential are often used to describe vitamins. These terms can be misleading. An essential vitamin is one that can only be found in the diet. A non-essential vitamin is also necessary for good health, but it can be manufactured by the body through other biochemical reactions. This however does not mean that non-essential vitamins are less important or that additional supplementation is never required. There are conditions in which the pathways in which these non-essential vitamins are formed are inefficient. Under these circumstances additional supplementation would be necessary. For example, a supplement and vitamin-like substance called Coenzyme Q is necessary for the proper cell function. The levels of CoQ diminish with age and are also diminished in people who take cholesterol lowering drugs called statins. In this case and there are others, external supplementation could be helpful in maintaining overall health. It is not possible to explain in detail all of the various vitamins, supplements, and vitamin-like substances in the scope of this article. I have thus focused on the most important and effective supplements; supplements that also are backed with a significant amount of credible research.

Vitamin D is Actually an Important Hormone: Deficiencies have been linked to various diseases, including some cancers

Vitamin D is known as a fat soluble vitamin. However, we have learned that it is actually a prehormone with extensive physiological effects. It is available in two forms: ergocalciferol, vitamin D2 and cholecalciferol, vitamin D3. Ergocalciferol (VitD2) comes from ergosterol, a plant sterol and yeast. Cholecalciferol VitD3, is synthesized in the skin via 7-dehydrocholesterol, a cholesterol precursor. Both forms are biologically inert (inactive) until they are hydroxylated (converted) in the body to Calcitriol.
Hydroxylation (conversion) of Vitamin D to calcitriol occurs in the kidneys. People with kidney failure may require Vitamin D in its active form. Vitamin D3 is significantly more potent and effective in humans.

Few foods naturally contain Vitamin D and the ones that do have been fortified. Brief exposure to sunlight is the best way to get Vitamin D. Skin exposure to the sun provides as much as 80% to 90% of the body's Vitamin D stores. In northern latitudes sun exposure particularly in the winter months may not be sufficient to cause Vitamin D synthesis in the skin. Sunlight intensity depends on latitude, altitude, season, cloud cover, ozone levels, etc. The capacity of UVB mediated Vitamin D synthesis is huge. Six days of casual sunlight exposure without sunscreen can make up for 49 days of no sunlight exposure. Skin pigmentation affects Vitamin D synthesis. A light-skinned person in northern latitudes wearing a bathing suit receives about 10-20,000 units of cholecaliferol in 10-12 minutes of peak July sun. A darker skinned person would require 30 minutes and an African-American 120 minutes for their skin to produce the same amount of Vitamin D.

African-American infants who are exclusively breast fed are at higher risk for Vitamin D deficiency and Rickets. Sun exposure three times a week for a period of time ( 25% of that which would cause a mild sunburn) will produce adequate amounts of Vitamin D.

Factors that affect Vitamin D levels:

Insufficient sun exposure
Reduced skin synthesis
Lower dietary intake
Impaired intestinal absorption
Decreased metabolism by the kidneys to active form of Vitamin D
(this condition increases with aging)
Vitamin D receptors decrease with age (serious concern for the elderly)
Obese people may have reduced serum Vitamin D levels and reduced
bioavailability. It seems the Vitamin D is sequestered into body fat
and unavailable.

Vitamin D regulates serum calcium and phosphorus concentrations. It enhances the efficiency of the intestinal absorption of calcium. Calcitriol (active form of Vitamin D), also has effects in the brain, heart pancreas mononuclear cells, activated lymphocytes, and skin.

Vitamin D increases muscle strength and neuromuscular function in addition to strengthening bone. It increase protein synthesis (700-800 units/day).

Vitamin D seems to have immunosuppressant activity, beneficial in autoimmune disorders like Rheumatoid Arthritis and Multiple Sclerosis. Evidence suggests that it improves respiratory disorders. There is an association between levels of 25-hydroxy vitamin D serum levels and pulmonary function. It might be involved in remodeling lung tissue. It could also decrease immune mediated inflammation in the airway.

Vitamin D deficiency is linked to an increase risk of falls. Taking Vitamin D supplements reduces falls by 22% in the elderly. Some studies showed that this benefit is independent of calcium supplementation.

A dose of 800units or higher is necessary for it to be effective. Interestingly, researchers believe that Vit D prevents falls by decreasing body sway and decreasing systolic blood pressure rather than increasing bone mass strength. Until now Vitamin D has been seen as a mere adjunct to calcium supplementation, but it is necessary and effective in it's own right.

Studies show that individuals with higher levels of vitamin D serum levels (25mol/L) concentrations have a significantly lower incidence of certin cancers, particularly gastrointestinal. In clinical trials, women taking calcium (400-1500mg/day with 1,100units of vit D3 had a 60% lower risk for developing cancers of various types.

Long term vit D supplementation decreases the risk of Multiple Sclerosis in women by 40%. Again the effect is dose dependent in this case a minimal dose of 400units/day. In addition, when vit D levels were measured in the general population the higher the level the lower the chances of developing Multiple Sclerosis (50nmol/L). Scientists suspect that this may be one of the reasons why the rate of MS is higher the further you are from the equator.

A large trial showed that women with lower levels of vit D have a higher risk of being obese, yet another reason to take vit D. When combined with calcium it helps maintain a healthy weight baseline. Effective doses are between 800-2000units/day.

Cautions: If you are using topical vitamin D creams you must consult your physician before taking vitamin D orally. Topical vitamin D is absorbed. Cimetidine (Tagamet) can decrease active vitamin D levels, particularly in patients with liver or renal insufficiency.

Omega-3: "An Omega a Day Helps Keep the Doctor Away"

There are several Omega-3 fatty acids. The two most commonly taken are DHA(docosahexaenoic acid) and EPA(eicosopentaenoic acid).

DHA is a polyunsaturated fatty acid that is found in tissues of marine animals. It is converted to EPA in humans. DHA competes with arachidonic acid for inclusion in cyclooxygenase and lipoxygenase pathways (substances responsible for inflammation). This competition may be responsible for its anti-inflammatory effect.

It reduces serum triglycerides (important in coronary artery disease). Increases fasting insulin and glucose concentrations(important for diabetes). It increases HDL (good cholesterol) by about 12 percent. It has an additive affect in reducing symptoms associated with schizophrenia and recurrent unipolar depressive disorder. The ethyl form of EPA is especially effective in depression (1gm twice a day). It slows weight loss in cachectic cancer patients. There is some evidence that suggests it to be helpful in prostate cancer.

It plays a key role in neural and synaptic membranes. These functions play a key role in learning and memory function. It is essential in healthy neurological development of infants. It is found in breast milk but not in standard infant formula. Supplementation is recommended for pregnant women beginning at week 15 (1.2gm-2gms/day).

It has been recommended for age-related macular degeneration, coronary disease, psoriasis(as an IV injection), hyperlipidemia, ADD, Alzheimer's. May also be beneficial in Multiple Sclerosis for its anti-inflammatory activity as well as its role in healthy neurological function.

The standard total Omega-3 fatty acid dose is 1800mg per day. It usually comes as a combination of EPA 350mg/DHA 200mg.

It is now well known that many of our diseases are in part a result of or are exacerbated by inflammation. Poor diets (high in saturated fatty acids and high glycemic index foods) as well as lack of adequate exercise play a significant role in the increase in inflammation in our bodies. Inflammation is a healthy response of the body to injury, but is problematic when it becomes chronic inflammation artificially produced by poor diet and a sedentary lifestyle. This inflammation affects our muscles, our vascular system and our neurological system, as well as our organs. Omega-3 fatty acids seem to block the inflammation pathway and help minimize subsequent damage. In addition to taking Omega-3's you should also minimize high glycemic foods in your diet. These include processed foods such as white sugar, white bread, pasta, etc. When we ingest high glycemic foods our pancreases release insulin and insulin is involved in a wide range of hormonal cascades which in turn cause inflammation.

CoEnzyme Q: "The Little Engine That Can"

Coenzyme Q (CoQ) is a staple for cardiovascular disease therapy in Japan, Europe and Russia. It is a vitamin like compound that is present in most cells of the body. The heart, liver, kidney and pancreas have especially high concentrations of CoQ. It is fat soluble and is a potent antioxidant. It is a membrane stabilizer (keeps the cell healthy and intact), it's a cofactor in metabolic pathways (a necessary enzyme in biochemical reactions in the cell) particularly in the production of adenosine triphosphate (ATP) in oxidative respiration (basically it plays an essential role in cell energy production).

The CoQ that is formulated in soybean oil appears to have superior bioavailability(easily absorbed by the body) compared to other formulations. Coenzyme Q increases HDL (good cholesterol), vitamin E, vitamin C, and actually decreases LDL (bad cholesterol).

So why and when do we need to supplement CoQ? Well the why is pretty evident. It is essential for overall good health. Coenzyme Q levels decline with age, declines with certain diseases(Congestive Heart Failure, Hypertension, Periodontal disease, certain muscular diseases and AIDS), and declines when taking certain drugs(such as beta-blockers and statins which are cholesterol lowering drugs; these drugs block the synthesis of cholesterol as well as CoQ).

In addition to the diseases already mentioned, CoQ supplementation may be beneficial in the following diseases as well: Parkinson's and Huntington's. It appears that these diseases might be caused by impaired function of the mitochondrial electron transport chain and particularly the mitochondrial enzymes, Complex I and Complex II (the mitochondria is like the cell's engine, the place where all the energy is produced).

CoQ might also prevent cardiotoxicity caused by phenothiazines (certain antipsychotics), tricyclicantidepressants, doxorubicin (chemotherapy). Some studies show that it may have some immunostimulatory activity in breast cancer.

It may also help in reducing migraine severity and increase exercise tolerance as well as helping with fatigue in Multiple Sclerosis.

As you can see there are various scenarios in which serum levels of CoQ are reduced and you can also see how important and essential it is to overall health. Every reaction in our body requires energy and CoQ is an essential part of that process. Dosing varies depending on which condition is being treated. Generally it is dosed at 100-200mg per day.

Folic Acid as Cinderella and Homocysteine as the Evil Stepmother

Folic Acid as Cinderella and Homocysteine as the Evil Stepmother
By: Cristina Berard, RPh, MEd

Folic acid or folate as it is also called, is found in green leafy vegetables. Folate from vegetables is about 40-50% less bioavailable than synthetic folic acid, which is almost 100% bioavailable. After it is absorbed by the body it is converted into tetrahydrofolate. Tetrahydrofolate based coenzymes play a major role in intracellular(within the cell) metabolism. Folic acid reduces errors to DNA and prevents replication errors. Folate deficiency disturbs the cycling of the cells and induces and increases the rate ofcell aptopsis (cell death). It is involved in the metabolism of homocysteine (high levels cause inflammation). Low levels of Folate are associated with an increase plasma homocysteine levels. High levels of homocysteine (hyperhomocysteinemia) is a risk factor for coronary, cerebral, and peripheral atherosclerosis; recurrent thromboembolism; deep vein thrombosis; myocardial infarction; and ischemic stroke.

Why are high homocysteine plasma levels a risk factor for certain diseases? The mechanism of action isn't fully understood, but it might include vascular endothelial cell damage(deterioration of the blood vessels), impaired endothelium dependent vasodilation (blood vessels don't dilate properly) due to reduced nitric oxide activity, arterial stiffening due to increase in oxidation(arteries become stiff) and arterial deposition of low density lipoproteins (LDL cholesterol deposits in the lining of the artery), increase of platelet adhessiveness (blood thickens becomes less viscous), and activation of the clotting cascade (increase in clots formed in the vessels).

All vitamins are essential and play important roles in metabolic pathways. Folic acid is an especially important vitamin. The following description of it's role may at times be a bit technical, but it is important in helping you to understand just how imperative it is to ensure that you are not deficient in folic acid or in any steps along the way.

Homocysteine is metabolized via two pathways. One is called "remethylation" the other "transsulfuration".

Homocystein-----------------------> methionine

This reaction is facilitated by folate and Vitamin B12 (cofactors). Without these two cofactors, this processes would not take place and homocystein would remain in tact, thus increase homocystein levels in blood stream. There is another factor that can impede this process. Some people homozygous fo the mutations of the gene MTHFR(5,10 methyltetrahydrofolate reductase). This is an enzyme involved in the conversion of homocysteine to methionine. When you are homozygous for this gene most often you need to take higher doses of folate, usually 1mg per day.

Transsulfuration usually occurs after an individual ingests a meal high in animal protein (a methionine load).
via pyrodoxine(vit B6)

Deficiency of pyrodoxine impairs the pathway raising homocysteine levels as well. In addition to folic acid, vitamin B12 and B6 are important for successful conversion of homocysteine.

What does all of this mean and why is it important to health? Well plays an important role in pregnancy and the healthy development of the fetus. Low levels are associated with neural tube defects in the fetus.

Low levels might play a role in Alzeihmers Disease. It seems to be associated with atrophy of the cerebral cortex.

Homocysteine is thought to be neurotoxic, causing DNA damage and cell apoptosis which is associated with functional and mental deterioration in the elderly.

Folic acid deficiency is common in people with depression. Low levels have been linked to poor response to antidepressant treatment.

Folic acid is required for the conversion of homocysteine------->SAMe. SAMe in turn is associated with an increase in serotonin turnover, increase in dopamine, and norepinephrine levels. All of these play a role in mood.

When you go to the pharmacy, you will find that there are individual B vitamins and then there are products that provide a combination of all B vitamins. The previous pathways might have given you a clue as to why these B vitamin complexes are so popular. Various B vitamins played a key role in these homocysteine conversion pathways. Where folic acid is the work horse, the other B vitamins are its helpers. Just like Cinderella was the hard worker of the family she couldn't have made it to the ball without her little helpers. By working together they were able to stop the evil stepmother (homocysteine) from getting her way.

Folic acid supplementation is helpful in treating and or preventing the following conditions: End-stage renal disease, hyperhomocysteinemia (11 micromoles/L or higher), methotrexate toxicity, neural tube defects, breast cancer, colorectal cancer, depression, Alzheirmers, risk of cervical cancer, cognitive function, infertility, and restless leg syndrome.

Typical doses are: 250mcg-1000mcg/Day
Severe disorders and under medical supervision(1000-5000mcg/Day)