Monday, May 25, 2015

Vitamin Poisoning: Are We Destroying Our Health with Hi-Potency Synthetic Vitamins?

Vitamins are readily available and sold in many different formulations, they're also added to common foods such as dairy, cereals, nutritional shakes and baking flour. We were taught to believe that vitamin supplements are beneficial and indeed under certain circumstances, such as with immuno deficiency diseases, vitamin supplementation regiments have shown to be helpful in relieving symptoms similar to drug administration. What we haven't been told is that in large dosages, as commonly prescribed by physicians or recommended by vitamin manufacturers, vitamins can become overwhelmingly toxic and the same vitamin treatment that potentially benefit sick individuals may actually devastate healthy individuals. To understand how vitamin poisoning occurs, we need to examine the three following issues: first, why so many of us become vitamin junkies? Second, how this very compulsive public need to shove in megadosages of vitamins has been exploited by the vitamin industry? And third, what are the real effects of vitamin supplementation on our cells, tissues and overall health?
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The need to take vitamin supplements

There is a widely held perception that human diseases are largely caused by vitamin deficiencies and therefore, supplementation with megadosages of vitamins can be beneficial in preventing disease. This view is not fully supported by medical evidence, nonetheless it is still propagated and has been explored by commercial interests such as for example, the inclusion of vitamin C in cold remedies, the addition of vitamin A and D to milk products, the enrichment of oils and margarines with vitamin E, the addition of vitamins to nutritional shakes and the non-regulated sales of vitamin A and E supplements.

There are plenty of articles that encourage megadosage vitamin treatment. Generally speaking, virtually all available information on vitamin supplementation (as provided by supplement companies) attack the minimum recommended daily allowance (RDA) for vitamins as too low. Regardless to the undeniable evidence that the human body is not programmed to utilize vitamins in maximum potencies, but rather in optimum potencies (sometimes below the minimum RDA), the industry wants you to believe that high potencies of vitamins yield better results.

We have been told repeatedly that vitamin overload such as with vitamin C or vitamin E isn't just beneficial in preventing the common cold, but also effective in killing cancer cells, chelating heavy metals, curing blood sugar disorders and counteracting aging. Our society has been trained to think in military terms when dealing with health issues. We habitually use terms such as "fighting illness", or "burning fat". It is perhaps understandable that there is a widely held perception that high potency vitamins are more powerful with a stronger capacity to "kill" disease than low potency vitamins. Most people today truly believe that high potency vitamins are superior to low potency vitamins regardless to how they're made - whether they're synthetically produced from chemicals or naturally extracted from food sources. Consequently, we have been becoming addicts to vitamin megadosages and the vast majority of us are not even aware of this. As you'll soon see, vitamin abuse is a serious issue that requires very close attention.

Can we do well without using vitamin supplements?

Apparently, in today's world it's virtually impossible to do well without nutritional supplements. Supplementation often presents the only practical means to grant an adequate intake of nutrients. Due to soil depletion, industrial food processing, storage conditions and often low accessibility to fresh nutrient-dense food, it becomes imperative to supplement our diet with vitamins and other essential nutrients which are missing in our food. And the people who need supplementation most, are those under an increased oxidative stress including people routinely engaged in intense physical training, people with immuno-deficiency diseases, and the elderly. Antioxidant nutrients have shown to help lower the metabolic stress caused by exercise or disease and thus protect cells and tissues from oxidative damage.

Nonetheless, we need to know how to make the right choices. Not all nutritional supplements are as beneficial as claimed and an excess of any substance including vitamins can be potentially as harmful as its deficiency. We'll continue with this soon, but for now let's examine the theory behind the usage of synthetic vitamins.

The orthomolecular theory

There is a growing school of nutritionists called orthomolecularists who argue that there is no difference between a "synthetic" and a "natural" vitamin molecule. According to this theory, biologically identical (bioidentical) molecules are indistinguishable from those synthesized by plants or animals. The orthomolecular theory (ortho-right) claims that we must support our bodies with the "right molecules" that are required to sustain life and that receptors on the surface of animal cells control the uptake of individual molecules regardless of how or why these molecules appear in the blood stream... Though lacking scientific substantiation, this theory has been adapted by medical authorities who recommend synthetic vitamin supplements, containing large concentrations of isolated vitamin molecules to serve as alternative medicine.

Millions of people today are taking vitamin supplements as the only means to prevent nutritional deficiencies, believing that it actually compensates for poor eating habits and bad diets. The highest pound-to-pound vitamin consumers are fitness advocates, athletes, the sick and the elderly, who have been told that their vitamin requirements are higher than normal and therefore require larger dosages. What remains largely overlooked is one single fact: there is no evidence that people who take vitamin supplements are doing better than those who don't. In fact, there are some indications that vitamin supplementation may actually shorten life span and may even increase cancer probability, such as in the case of synthetic vitamin E and beta carotene. As you'll soon see, the evidence shows that vitamin supplements can become toxic to the body in the following circumstances:

 - if they're synthetically produced

 - if taken in overly high unnatural dosages.

Poisonous vitamins

Up until recently, it has been commonly assumed that only fat soluble vitamins can potentially become toxic. Since fat soluble vitamins A, E, D, and K can be stored by the body and accumulate in overly high toxic levels when taken in large dosages, it has been recommended to be cautious with their intake, a recommendation which nevertheless has been ignored by vitamin manufacturers who keep selling formulas with high contents of fat soluble vitamins.

Vitamin poisoning is not a simple problem. The issue involves lots of misinformation and misunderstanding. The information provided by vitamin manufacturers do not always reveal the truth, certainly not the whole truth. People today are easily fooled to believe that it's worth popping pills that can yield hundreds of times greater vitamin concentration than real food. What the public hasn't been fully aware of is that the human species evolved to beneficially utilize nutrients only as they naturally occur in food and not in any other way.

The early human diet was largely vegetarian, humans have adapted to utilize nutrients and vitamins from plant sources in the safest, most efficient way and at exactly the right concentrations needed for the body's metabolic needs. Human biology is undoubtedly vegetarian-oriented. We all carry an inherent enzymatic capacity to convert complex plant nutrients into bioactive compounds, vitamins, minerals and antioxidants, all of which are utilized by the body through a tightly feedback control. This is how we evolved to be. We can safely utilize natural plant carotenes into vitamin A, we can safely optimize our vitamin D from germs and seeds as well as through exposure to UV sunlight and we can safely utilize vitamin E from eating raw nuts and seeds, without any risk of toxicity.

However, as great as our capacity to utilize natural nutrients from food is, we are lacking the capacity to properly utilize synthetic nutrients derived from chemical processing. The human body can't regulate the absorption of synthetic vitamins, neither can it optimize their levels. Here is what likely occurs when synthetic vitamins are administered. The highly bioactive, chemically processed vitamin molecules bypass the body's natural enzymatic pathways, giving the body the signal that its vitamin pool is fully loaded. After synthetic vitamin administration, the body is tricked to believe that it doesn't need to utilize more of the same nutrients from food. Consequently, the enzymes that normally utilize complex plant nutrients into vitamin molecules are inhibited and the body is losing its ability to fully assimilate food's nutrients, as well as the capacity to regulate and optimize healthy vitamin concentrations. In reality, synthetic vitamins are received by the body as drugs and like all drugs, they can potentially disrupt normal metabolic functions often with devastating side effects.

Toxicity Side Effects of Excess Fat Soluble Vitamins

Vitamin A: abdominal pain, vomiting, headache, lethargy, eczema, patchy hair loss, edema, anemia, respiratory tract infection, chronic liver disease

Vitamin E: allergic reaction, breathing impairments, swelling of the tongue, fatigue, headache, nausea, blurred vision, excessive bleeding (anticoagulation due to inhibition of vitamin K), increased oxidative stress, increased hypertension, decreased life span

Vitamin K: supplementation with a synthetic form of vitamin K Menadione has been associated with liver damage. Some reports indicate a significant association between high intramuscular levels of vitamin K and cancer.

Vitamin D: even though vitamin D poisoning is rare, toxicity can occur under certain medical conditions such as primary hyperparathyroidism, tuberculosis and lymphoma. Note that vitamin D is completely safe when produced by the body itself through UV sunlight exposure.

As for the water soluble vitamins C and Bs, these have been generally considered safe simply because water soluble vitamins are not stored by the body. Since any excess of water soluble vitamins is excreted in the urine, they presumably can't accumulate in toxic levels and therefore are regarded as safe. But are they safe indeed? Let's review how safe the water soluble vitamins are, starting with the one considered the safest of all - vitamin C.

Vitamin C - Cure or curse?

The belief that megadosages of vitamin C can cure the common cold and prolong life was given credence by the American scientist Linus Pauling (1901-1994). The basic premise of his advocation of vitamin C in large dosages was that there is somehow a "design flaw" in the human genome which disables us to produce vitamin C like other animals. According to Pauling and his advocates, we need to compensate for our genetic fault with 10,000 - 12,000 mg of vitamin C daily as adults, to prevent or cure disease.

The recommended daily allowance (RDA) of vitamin C is 60 - 90 mg per day. Men are advised to consume more vitamin C than women and individuals who smoke or are engaged in intense physical activities are encouraged to consume more vitamin C than average adults. This recommendation is due to the fact that smoking and exercise deplete vitamin C in the body, leaving cells vulnerable to oxidative damage. The upper intake level for vitamin C was set at 2000 mg a day for adults by the Food and Nutrition Board in 2000.

The vitamin C molecule, ascorbic acid (ascorbate) seems to be critically important to all animals and humans. It is vital to the production of collagen, it helps recycle vitamins A and E, it helps potentiate iron absorption and support adrenal functions particularly during times of extreme stress, but most notoriously, vitamin C prevents and cures scurvy disease, even in small potencies such as those naturally occurring in a single lemon or an apple. Scurvy is rarely seen today except in alcoholics or extreme cases of drug addictions, eating disorders or starvation. The disease causes bleeding and inflamed gums, loose teeth, poor wound healing, easy bruising, joint pain, muscle wasting, and a total metabolic decline with mortal consequences if untreated.

In theory, vitamin C ascorbate can help cure ailments, build tissues, counteract stress and promote great health, this is at least how ascorbic acid has been advertised. But what seems great in theory isn't always as great in reality. Let's examine the actual effects of ascorbic acid supplementation in real life. The following information is based on recent studies, I choose to feature the following reports since I believe they may help put the record straight regarding ascorbic acid supplementation in particular, and synthetic vitamins and their potential pathology, in general.

Ascorbic acid supplementation impairs muscle's mitochondrial function and adaptability to exercise.

A recent article in the American Journal of Clinical Nutrition (Vol. 87, No. 1, 142-149, January 2008) reveals that supplementation with vitamin C ascorbate devastates the muscle, causing impairment in mitochondrial function, loss of endurance, and inhibition of the body's own antioxidant enzymes superoxide dimutase (SOD) and glutathione peroxide. Levels of SOD and glutathione enzyme are known markers of health and any substance that causes a substantial decrease in the levels of these essential antioxidant enzymes, disrupts the body's immune system, lowering the capacity to resist infection and disease. In this case, rather than being a beneficial antioxidant, vitamin C ascorbate has shown to work as an adverse pro-oxidant.

The study featured in the article was designed to examine the effect of vitamin C on training efficiency in animals and humans. The researchers were aware that ascorbic acid supplementation is highly popular among exercise practitioners. The reason: since intense exercise increases oxidative stress in the muscle (as indicated by increases in peroxidation of lipids, proteins and DNA), it then has been assumed that administration of the antioxidant vitamin C ascorbate may help protect the muscle from oxidative damage. But again, in real life things often occur differently than in theory and in this case, the findings leave no place for a doubt: ascorbic acid supplementation shatters muscle performance by actually increasing oxidative stress and suppressing some critical cellular mechanisms of adaptation to exercise.

Are all forms of vitamin C supplements potentially damaging to the muscle?

Certainly not. Unlike the synthetic vitamin C, its natural equivalent is both healthy and safe. Natural vitamin C as originally occurring in plants isn't just beneficial to the muscle, it is actually essential to the whole body.

Humans and primates can't produce vitamin C and therefore must ingest it from a dietary source. The human diet evolved to be largely dependent on vitamin C rich foods, particularly fruits and vegetables and like other primates andapes, we have evolved to actually thrive on these natural vitamin C sources. Why then, vitamin C ascorbate induces toxic effects instead of beneficial effects? Again, the reason: human biology has never evolved to accept synthetic vitamins. In its natural form, vitamin C has a different design than the synthetic vitamin. The natural vitamin C molecule never occurs in isolated form, but rather accompanied by complex nutrients which apparently are essential for vitamin C's bioactivity. The synthetic ascorbate however, appears in an isolated form, often in overly high concentrations which the human body hasn't evolved to properly utilize.

To be viable, vitamin C should be supplemented as it naturally occurs in food. When choosing a vitamin C supplement, make sure it is indeed derived from a natural food source and attached to its nutritional cofactors.

To further understand how synthetic vitamins become toxic to the body, we need to take a look at how the human survival apparatus has evolved to work - how the very bio-mechanisms that have kept our species alive on this planet really operate.

Stress resistance, starvation resistance and longevity

It has been widely established that the human body is not inherently programmed for today's world, but rather designed for a primordial world that existed many thousands of years ago. Anthropological evidence indicates that the human genome hasn't changed at all in the past fifty thousand years, we still carry the same genes of our cavemen ancestors but apparently the world that we live in today is different than the world we have originally adapted to. Staying alive during primordial times required the skills to actively survive, humans evolved to being capable of enduring intense physical tasks, gathering or hunting for food, fighting foes and beasts or fleeing if necessary. Humans also evolved to be capable of enduring periodical hunger due food scarcity. Our "primitive" genome is programmed to actually thrive in rugged conditions which mimic primordial hardship. We all carry survival genes (also called longevity genes) that increase our ability to survive by upgrading our energy utilization, strengthening our muscle, improving our capacity to resist stress and starvation, and even elongating life. And these genes are triggered when we're routinely and repeatedly confronted with physical challenges (exercise) or forces to endure food scarcity (undereating or fasting).


Animal studies have indicated that starvation resistance is one of the most important evolutionary traits linked to longevity. This life extending trait is attributed to a certain genetic phenotype which likely evolved to increase survival probability during times of food scarcity. Note that there is a thin line that separates between scarcity of food and lack of food. There is obviously a huge difference between eating less and not eating at all. Food shortage and starvation are problems that existed in the past and still exist today, but can be resolved by restoration of agricultural and industrial means to yield sufficient food supply. The main problem however, that our western society faces today is not food deficiency, but rather excess of food and this problem remains largely unresolved.

Apparently, we have evolved to better survive in a world of scarce than in a world of plenty and for that matter, our bodies are inherently designed to get maximum nourishment from minimum food. This is likely an evolutionary feature that had enabled our early ancestors to overcome famine or food scarcity, which were common factors of life during primordial times.

The same may hold truth for human vitamin intake; our species has successfully thrived thousands of years on this planet, without a single vitamin supplement. Why have we been so largely ignoring this simple fact? Though there are good reasons today for supporting our diet with vitamin supplementation, we need to be aware of one thing: humans have never evolved to be supported by megadose vitamins. We are inherently more frugal than we think. We do better living off the land, eating scarcely from a few accessible choices of seasonal foods, than living off the supermarket, eating excessively from multiple choices of food products. Excess is toxic and inflammatory. We can become fat, bloated and sick from excess calories and similarly we can be poisoned and sickened by excess vitamins.

Humans carry genetic codes that improve survival capabilities when routinely challenged by intense physical stress or food scarcity. Scientists speculate that these gene phenotypes give us a great evolutionary advantage. Both physical stress and lack of food are perceived by the body as survival challenges that need to be dealt with and in response, the body's survival mechanisms compensate us by upgrading our survival capabilities and extending our lifespan. Given all this, we should be aware that anything which contradicts our "active survival" program, anything that causes excess or imbalance in our body, anything that down regulates the genes that make us thrive, should be avoided or possibly counteracted.

How antioxidants turn pro-oxidants

The knowledge of how the body's survival mechanisms operate is a key to understanding how the body utilizes nutrients and vitamins. The truth is that stress is a critical factor of life. Even though, the concept that stress is beneficial and essential to life (like yin to yang) remains highly controversial.

One of the most critical elements of survival is the sustainability of the body's metabolic environment. The body is highly sensitive to changes in its metabolic environment (homeostasis) - capable of detecting fluctuations in blood sugar, decreases or increases in cellular energy and most importantly, it is highly sensitive to changes in cellular levels of oxidative free radicals. We have been told that free radicals are the bad guys that destroy our cells and tissues, whereas antioxidants are the good guys that save us from the harmful effects of these oxidative bad guys. But is it true?

Since this is a complex issue, it is imperative to reconsider this assumption and reexamine the facts. The truth is that free radicals can be damaging when accumulated in overwhelmingly high cellular levels but not always. In many cases such as with exercise, they actually serve as signals to improve adaptation of muscle cells to physical hardship. A certain threshold of cellular free radicals is needed to "tone" the muscle and incredibly, this very threshold of free radicals in the muscle cell is what keeps the muscle's own energy system and antioxidant defenses in tact.

Low threshold concentrate of free radicals in the muscle, such as after short term exercise, is beneficially acting as a signal to enhance defenses rather than being deleterious. The free radicals threshold in the muscle is an essential part of the mechanism that makes exercise so beneficial to human health.

Two of the most notable effects of exercise are I: the increased expression of longevity promoting antioxidant enzymes is skeletal muscle (mitochondrial SOD and gluthatione peroxidase GPx) and II: the increase in muscle mitochondrial content. It is now known that endurance capacity is dependent mainly on mitochondrial content and antioxidant defenses of skeletal muscle.

And here is the point: these awesome, beneficial effects of exercise on muscle conditioning can be seriously compromised by synthetic antioxidant supplements. In the case of vitamin C, what scientists have been realizing is that ascorbic acid supplementation, by all means devastates the muscle by overwhelming the muscle's minimum free radical threshold and thereby decreasing both mitochondrial biogenesis and antioxidant capacity in the cell.

Ascorbic acid is not the only vitamin supplement that potentially can devastate the muscle. In fact, several reports have shown antagonizing effects of other antioxidant vitamins as well. As early as 1921, it was shown that vitamin E supplementation in 400 iu/day (a commonly used dosage) caused an unfavorable decrease in endurance performance. In 1996 and 1997, a Scandinavian journal published 2 reports showing the adverse effects of antioxidant supplementation (Ubiquinon-10) on high intensity training performance. In 2001, Coombes et al reported that supplementation with vitamin E and alpha lipoic acid depressed muscle contractile force in animals. One year later, it was shown that supplementation of racing greyhound dogs with 1g vitamin C/day for 4 weeks significantly slowed their speed.

Given all this, the common practice of taking ascorbic acid and other synthetic antioxidant supplements for both health related and physical performance related improvements, should be seriously questioned.

The B vitamins syndrome

B vitamins are water soluble compounds, serving as catalysts and cofactors in multiple enzymatic processes involved in energy production, hormones synthesis, neurotransmitters activation and many other critical metabolic functions. Because of their great appeal, B vitamins are commonly added to food stuff for enrichment of nutritional content. However, even though largely regarded as safe, B vitamins are now gaining the reputation as risky substances, particularly when applied in large concentrations. The most notable risk involving a B vitamin supplement is its potential excess, which ironically can cause depletion of other B vitamins, as well as toxic side effects.

For instance, excessive vitamin B1 can deplete other B vitamins, disrupt insulin and thyroid production. Excessive vitamin B3 has shown to cause liver damage. Megadosages niacin have also shown to adversely affect individuals who suffer from glaucoma, gout, liver disease and peptic ulcers. Note that megadosages niacin have been commonly prescribed today as an alternative medicine to lower cholesterol levels. Excess of synthetic vitamin B6 pyridoxine has shown to cause liver damage when used in long term "therapeutic" dosages (over 200 mg/daily). These so-called therapeutic potencies of B6 are currently available over the counter in stores nationwide. Even folic acid, which is regarded as safe and highly beneficial, could turn to be toxic in high doses (5-10 mg) with symptoms including bloating, nausea and upset stomach. High dosages of folic acid may also result in increased occurrence of seizures among individuals suffering from epilepsy.

Why the water soluble, presumably safe B vitamin supplement that can be exerted via the urine are nevertheless risky? Because as we've seen, synthetic vitamins lack the natural design of food based vitamins. Again, the body can only utilize vitamins as they naturally occur in food, regardless to whether these are water soluble or fat soluble. In their naturally occurring state, vitamins always appear in a group, balanced with other nutritional cofactors and in the right biological concentrations. In its natural form such as in plant food, a B vitamin is not only 100% safe and non-toxic, it is very unlikely that it will ever be absorbed in an excess.

Contrary to natural vitamins, their isolated synthetic equivalents are inherently problematic, There is no single vitamin manufacturer in the world that has yet figured out how to provide us with what nature has been providing us since the genesis of the human species: The right balance and complexity of nutrients. Regardless to how fancy, sophisticated and "advanced" a vitamin formula is, it can never be properly balanced and safely nourishing unless it is made with all naturally occurring ingredients as in food.

How to detect the difference between natural and synthetic vitamin supplements

The most notable difference between natural and synthetic vitamin supplements is in their claimed potencies. Natural vitamins as in plant foods are never highly concentrated. Nature provides us with balance, complexity and bioavailability but not with a high potency. Conversely, synthetic and crystalline (chemical isolated from natural source) vitamins do appear in high unnatural potencies.

When examining products labeled as natural vitamins, note that labels of truly natural food based vitamins, should indicate the exact natural source from which each of the vitamins is obtained. Simply put, if the vitamin concentrations are high and/or their natural sources aren't listed, most likely these vitamins are synthetic. Chemical sources for synthetic vitamin supplements include petrochemicals, coal tar, chemically manipulated sugar and inorganic minerals.

Conclusion

We require food and vitamins to survive. Due to common nutrient deficiencies as well as inaccessibility to fresh, nutrient dense food, we need to supplement our body with vitamins and other essential nutrients. However, what many of us have been failing to realize is that in order to thrive, our bodies require optimum levels of nutrients, as naturally occurring in food and not maximum levels of nutrients, as chemically isolated or synthetically produced by the industry. It may take another decade or perhaps another century for scientists to fully understand the magnitude of benefits we get from the multiple complexities of whole food's nutrients and accordingly establish undeniable principles upon which the human diet should be based. Until then, we need to rely on the logic behind our life. Biology means the "logic of life" and this logic clearly indicates that our health is programmed to thrive on food nutrients, not chemicals.

For more information, please visit http://www.defensenutrition.com

REFERENCES

Gomez-Cabrera MC, Domenech E, Romagnoli M, Arduini A, Borras C, Pallardo FV, Sastre J, and Vina, J. Oral administration of vitamin C decreases muscle mitochondrial biogenesis and hampers training-induced adaptations in endurance performance. Am J Clin Nutr. 2008 Jan;87(1):142-9.

Berger TM, Polidori MC, Dabbagh A, et al. Antioxidant activity of vitamin C in iron-overloaded human plasma. J Biol Chem 1997;272:15656-60.

Burton GW, Traber, MG, Acuff RV, Walters DN, Kayden H, Hughes L, Ingold, KU. (1998). Human plasma and tissue alpha-tocopherol concentrations in response to supplementation with deuterated natural and synthetic vitamin E. Am J Clin Nutr 67, 669-684.

Childs A, Jacobs C, Kaminski T, Halliwell B, Leeuwenhurgh C. Supplementation with vitamin C and N-acetvl-cysteine increases oxidative stress in humans after an acute muscle injury induced by eccentric exercise. Free Radic Biol Med 2001;31:745-53.

Coombes JS, Powers SK, Rowell B, et al. Effects of vitamin E and alpha-lipoic acid on skeletal muscle contractile properties. J Appl Physiol 200 1;90: 1424-30.

Close GL, Ashton T, Cable T, et al. Ascorbic acid supplementation does not attenuate post-exercise muscle soreness following muscle-damaging exercise but may delay the recovery process. Br J Nutr 2006;95 :976-81.

Davies KJ, Packer L, Brooks GA. Biochemical adaptation of mitochondria, muscle, and whole-animal respiration to endurance training. Arch Biochem Biophys 1981;209:539-54.

Facts about Vitamin A and Carotenoids, from the National Institates of Health's Office of Dietary Supplements. 

Gomez-Cabrera MC, Borras C, Pallardo FV, Sastre J, Ji LL, Vina J. Decreasing xanthine oxidase-mediated oxidative stress prevents useful cellular adaptations to exercise in rats. J Physiol 2005;567:113-20.

Hathcock JN, Shao A, Vieth R, Heaney R (January 2007). "Risk assessment for vitamin D". Am J Clin Nutr 85(1): 6-18.

Huang HY, & Appel LJ. (2003). Supplementation of diets with alpha-tocopherol reduces serum concentrations of gamma- and delta-tocopherol in humans. Journal of Nutrition, 133, 3137-3140.

Levy. AP, Gerstein, HC, Miller-Lotan, R, Ratner, R, McQueen, M, Lonn, E, & Pogue, J. (2004). The effect of vitamin E supplementation on cardiovascular risk in diabetic individuals with different haptoglobin phenotypes. Diabetes Care, 27, 2767.

Malm C, Svensson M, Sjoberg B, Ekhorn B. Supplementation with ubiquinone-10 causes cellular damage during intense exercise. Acta Physiol Scand 1996;157:51 1-2.

Miller, ER 3rd, Pastor-Barriuso, B, Dalal, D, Riemersma, RA, Appel, LJ, & Guallar, E. (2004). Meta-Analysis: High-Dosage Vitamin E Supplementation May Increase All-Cause Mortality. Annals of Internal Medicine, 142.

Morh D, Stocker R. Selective and sensitive measurement of vitamin C, ubiquinol-10 and other low-molecular-weight antioxidants. in: Punchard NA, Kelly FJ, eds. Free radicals-a practical approach. Oxford, United Kingdom: Oxford University Press 2002:271-86,

Nielsen AN, Mizuno M, Ratkevicius A, et al. No effect of antioxidant supplementation in triathletes on maximal oxygen uptake, 31P-NMRS detected muscle energy metabolism and muscle fatigue. Int J Sports Med 1999 20: 154-8.

Manning PJ, Sutherland WH, Walker RJ, Williams SM, De Jong SA, Ryalls AR, & Berry EA. (2004). Effect of high-dose vitamin E on insulin resistance and associated parameters in overweight subjects. Diabetes Care, 27, 2166-2171.

Marshall RJ, Scott KC, Hill RC, et al. Supplemental vitamin C appears to slow racing greyhounds. J Nutr 2002;132(suppl):1616S-21S.

Shekelle P, Morton S, Hardy M. Effect of Supplemental Antioxidants Vitamin C, Vitamin E, and Coenzyme Q10 for the Prevention and Treatment of Cardiovascular Disease. Summary, Evidence Report/Technology Assessment: Number 83. AHRQ Publication Number 03-E042, June 2003. Agency for Healthcare Research and Quality, Rockville, MD.

Vieth R (May 1999). "Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety". Am. J Clin. Nutr. 69 (5): 842-56.

Vitamin A Toxicity from http://www.vitamindcouncil.org/newsletter/2008-december.shtml

Xavier Mertz (first documented death of Hypervitaminosis A after consuming a sled dog's liver during an Antarctic expedition)

Vitamin D Council (Vitamin A & D ratios and problems)

Watson WA, Litovitz TL, Klein-Schwartz W, et al (2004). "2003 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System". Am J Emerg Med 22 (5): 335-404.

Chippendale AK, Leroi AM, Kim SB, Rose MR. (1993). Phenotypic plasticity and selection in Drosophila life-history evolution. I. Nutrition and the cost of reproduction. J Evol Biol 6 171-193.

These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.

Information on this site is provided for informational purposes and is not meant to substitute for the advice provided by your own physician or other medical professional. You should not use the information contained herein solely for diagnosing or treating a health problem or disease, or prescribing any medication. 

B Vitamin Overdose Symptoms

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B vitamins are a set of nutrients that are essential for human life. The B vitamins, or B complex include vitamins B-1, B-2, B-3, B-5, B-6, B-7, B-9 and B-12. Respectively, these vitamins are also called thiamine, riboflavin, niacin, pantothenic acid, pyridoxine, biotin, folic acid and cobalamin. Normally, excess B vitamins are excreted by the kidneys, but high doses of vitamin B supplements can lead to an overdose.

Thiamine Overdose

Overdosing on thiamine, or vitamin B-1, is rare but can cause severe symptoms. Mild symptoms of an overdose include weakness and a headache, the American Pregnancy Association reports. In some cases, high vitamin B-1 levels can cause a rapid, irregular heart beat and low blood pressure. These symptoms can lead to cardiac problems. Some patients will develop a low blood pressure and convulsions.

Riboflavin Overdose

There are few potential side effects from high doses of riboflavin. The most serious side effects concern an increased rate of allergic reactions in patients taking high doses of riboflavin. Symptoms of allergic reactions include swelling of the face or tongue, hives and difficulty breathing, Drugs.com states. Consult a doctor if you develop these symptoms after taking vitamin B-2. Riboflavin can also cause a harmless yellow-orange discoloration of your urine.

Niacin Overdose

Overdosing on niacin, also called vitamin B-3, can lead to rare side effects. The most apparent symptom of a niacin overdose is a blurring of vision, the American Cancer Society says. This can be a sudden symptom that is disorienting and frightening. You may also experience gastrointestinal symptoms such as nausea, stomach pain and vomiting.

Pantothenic Acid and Biotin Overdose

Pantothenic acid, vitamin B-5, and biotin, vitamin B-7, are necessary for normal metabolism and the breakdown of proteins and carbohydrates. High doses of vitamin B-5 can cause severe diarrhea according to Medline Plus, a service of the National Institutes of Health. However, there are no known toxicities associated with biotin intake.

Pyridoxine Overdose

Toxic levels of pyridoxine have been known to cause a variety of muscular or nerve problems. You may experience burning pains, clumsiness, a loss of muscle coordination and even paralysis, the American Pregnancy Association reports. Vitamin B-6 toxicity can also cause rapid breathing and dyspnea

Folic Acid Overdose

Folic acid, or vitamin B-9, is dangerous when taken in high dosages. Normally, folic acid is given to help keep nerves healthy and ensure a healthy pregnancy. However, in doses greater than 15,000 ug per day, vitamin B-9 can cause damage to your central nervous system, the American Pregnancy Association warns. This may manifest as movement disorders, paralysis, pain or numbness.

Cobalamin Overdose

Excess intake of cobalamin, or vitamin B-12, may cause some symptoms in patients. You may develop blood clots, itching, diarrhea and serious allergic reaction, Medline Plus says. To avoid these symptoms, take vitamin B-12 as recommended by your doctor.


Vitamin Toxicity Symptoms

You can overdose on any vitamin supplement if you take it long enough and in high enough doses. Since only the fat-soluble vitamins---A, D, E and K---are stored in your body in greater-than-needed amounts, they are the ones mostly like to reach toxic levels. Vitamin D has the potential to be more toxic than any other vitamin. Vitamin E toxicity, on the other hand, is uncommon, and when it does occur, it is less serious than toxicity from vitamins A, D and K.

Skin and Hair Changes

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An overdose of the synthetic form of vitamin K used in supplements can cause red blood cells to burst and release their pigment, which will give the skin a yellowish cast. An overdose can also lead to brain damage. You might find vitamin K in multivitamin supplements, but since higher doses can quickly reach toxic levels, single-vitamin supplements are only available with a doctor's prescription.



Early signs of vitamin A toxicity include dry skin, hair, lips and eyes. In severe cases, the skin will start to peel. Though not technically toxic, too much vitamin A in the form of beta carotene can result in carotenodermia, a deep yellow pigmentation of the skin, including the palms of the hands and the soles of the feet. This is one of the few instances of vitamin overdose that can occur from consuming too much of a particular type of food. In this case, because beta carotene is not only a form of vitamin A but also a deep yellow pigment, that pigment can build up in the body if you eat too many carrots or other yellow-orange foods.

Digestive Discomfort

Very high doses of any vitamin, including water-soluble vitamins like niacin and vitamin C that are not stored in the body, are likely to cause some abdominal discomfort. These symptoms can include loss of appetite, nausea, diarrhea, vomiting and general digestive discomfort. 



When gastrointestinal symptoms appear with vitamin D toxicity, they may be the first signs of hypercalcemia, or too much calcium in the blood. One of the primary roles of vitamin D in the body is to facilitate and regulate calcium absorption into the body. When there is an overabundance of vitamin D, too much calcium is absorbed. Hypercalcemia can lead to organ damage.

Other Indications

With most vitamins, headaches, along with irritability, drowsiness and sometimes weakness will follow other signs of toxicity.



Severe vitamin B6 toxicity can result in a condition known as sensory neuropathy, which causes pain and numbness in fingers and toes and sometimes difficulty walking.



Frequent urination is a sign of vitamin D toxicity, and if overdosing continues, kidney stones and eventually kidney failure can occur.



Although it is unlikely, red blood cell breakage is possible with vitamin E toxicity as a result of the vitamin's interference with normal blood clotting activity in the body. There are usually no changes in skin color as with vitamin K, but hemorrhaging can result.

Thursday, May 14, 2015

sildenafil, Viagra, Revatio

DRUG CLASS AND MECHANISM: It has been estimated that impotence(erectile dysfunction, ED) affects 140 million men worldwide. Over half of all men with impotence are thought to have some physical (medical) cause. The remainder are believed to have psychogenic causes of impotence. Medical causes of impotence include diabetes and circulatory, neurological, or urological conditions.
Penile erection is caused by the engorgement of the penis with blood. This engorgement occurs when the blood vessels delivering blood to the penis increase the delivery of blood and the blood vessels carrying blood away from the penis decrease the removal of blood. Under normal conditions, sexual stimulation leads to the production and release of nitric oxide in the penis. Nitric oxide then activates the enzyme, guanylate cyclase, which causes the production of cyclic guanosine monophosphate (cGMP). It is the cGMP that is primarily responsible for the erection by affecting the amount of blood that the blood vessels deliver and remove from the penis.

Jafrum - Viagra Doctor
Sildenafil also reduces the pressure in the pulmonary artery in a serious condition called pulmonary arterial hypertension.
Sildenafil inhibits an enzyme called phosphodiesterase-5 (PDE5) which destroys the cGMP. Thus, sildenafil prevents the destruction of cGMP and allows cGMP to accumulate and persist longer. The longer cGMP persists, the more prolonged the engorgement of the penis.

PRESCRIBED FOR: Sildenafil is used for the treatment of erectile dysfunction of either organic (medical condition) or psychogenic (psychological) cause and for pulmonary arterial hypertension.
SIDE EFFECTS: Approximately 15% of persons taking sildenafil experience side effects. The most common side effects are:
Other important side effects include rare cases of sudden loss of hearing have been reported with phosphodiesterase inhibitors such as sildenafil, sometimes with ringing in the ears and dizziness. If changes in hearing occur, patients should discontinue their sildenafil and seek immediate medical attention.
PRESCRIPTION: Yes
GENERIC AVAILABLE:Yes
PREPARATIONS: Viagra is a blue, film-coated, rounded, diamond-shaped tablet that comes in 25, 50, and 100 mg tablets for treating impotence. Revatio comes in a 20 mg tablet and is used for treating pulmonary arterial hypertension.
STORAGE: Tablets should be kept at room temperature, 15 C - 30 C (59 F - 86 F).
DOSING: Sildenafil is rapidly absorbed. Maximum observed plasma concentrations are reached within 30 to 120 minutes (median 60 minutes) of oral dosing in the fasted state. When sildenafil is taken with a high fat meal, the rate of absorption is reduced, with an average delay in the time to maximal concentration of 1 hour.
DRUG INTERACTIONS: Sildenafil increases the effects of the blood pressure lowering medications. It also increases the blood pressure lowering effects of nitrates, for example, isosorbide dinitrate (Isordil), isosorbide mononitrate (Imdur, Ismo, Monoket), nitroglycerin (Nitro-Dur, Transderm-Nitro) that are used primarily for treating angina. Patients taking nitrates should not receive sildenafil.

Monday, May 11, 2015

Viagra

SIDE EFFECTS

The following are discussed in more detail in other sections of the labeling:
  • Cardiovascular [see WARNINGS AND PRECAUTIONS]
  • Prolonged Erection and Priapism [see WARNINGS ANDPRECAUTIONS]
  • Effects on the Eye [see WARNINGS AND PRECAUTIONS]
  • Hearing Loss [see WARNINGS AND PRECAUTIONS]
  • Hypotension when Co-administered with Alpha-blockers or Anti-hypertensives [see WARNINGS AND PRECAUTIONS]
  • Adverse Reactions with the Concomitant Use of Ritonavir [seeWARNINGS AND PRECAUTIONS]
  • Combination with other PDE5 Inhibitors or Other Erectile Dysfunction Therapies [see WARNINGS AND PRECAUTIONS]
  • Effects on Bleeding [see WARNINGS AND PRECAUTIONS]
  • Counseling Patients About Sexually Transmitted Diseases [seeWARNINGS AND PRECAUTIONS]
The most common adverse reactions reported in clinical trials ( ≥ 2%) are headache, flushing, dyspepsia, abnormal vision, nasal congestion, back pain,myalgia, nausea, dizziness, and rash.

Side Effects of Biagra by Jafrum

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
VIAGRA was administered to over 3700 patients (aged 19-87 years) during pre-marketing clinical trials worldwide. Over 550 patients were treated for longer than one year.
In placebo-controlled clinical studies, the discontinuation rate due to adverse reactions for VIAGRA (2.5%) was not significantly different from placebo (2.3%).
In fixed-dose studies, the incidence of some adverse reactions increased with dose. The type of adverse reactions in flexible-dose studies, which reflect the recommended dosage regimen, was similar to that for fixed-dose studies. At doses above the recommended dose range, adverse reactions were similar to those detailed in Table 1 below but generally were reported more frequently.
Table 1: Adverse Reactions Reported by ≥ 2% of Patients Treated with VIAGRA and More Frequent than Placebo in Fixed-Dose Phase II/III Studies
ADVERSE REACTION25 MG 
(N=312)
50 MG 
(N=511)
100 MG 
(N=506)
PLACEBO
(N=607)
Headache16%21%28%7%
Flushing10%19%18%2%
Dyspepsia3%9%17%2%
Abnormal vision†1%2%11%1%
Nasal congestion4%4%9%2%
Back pain3%4%4%2%
Myalgia2%2%4%1%
Nausea2%3%3%1%
Dizziness3%4%3%2%
Rash1%2%3%1%
†Abnormal Vision: Mild to moderate in severity and transient, predominantly color tinge to vision, but also increased sensitivity to light, or blurred vision.
When VIAGRA was taken as recommended (on an as-needed basis) in flexible-dose, placebo-controlled clinical trials of two to twenty-six weeks duration, patients took VIAGRA at least once weekly, and the following adverse reactions were reported:
Table 2: Adverse Reactions Reported by ≥ 2% of Patients Treated with VIAGRA and More Frequent than Placebo in Flexible-Dose Phase II/III Studies
ADVERSE REACTIONVIAGRA
N=734
PLACEBO
N=725
Headache16%4%
Flushing10%1%
Dyspepsia7%2%
Nasal Congestion4%2%
Abnormal Vision†3%0%
Back pain2%2%
Dizziness2%1%
Rash2%1%
†Abnormal Vision: Mild and transient, predominantly color tinge to vision, but also increased sensitivity to light or blurred vision. In these studies, only one patient discontinued due to abnormal vision.
The following events occurred in < 2% of patients in controlled clinical trials; a causal relationship to VIAGRA is uncertain. Reported events include those with a plausible relation to drug use; omitted are minor events and reports too imprecise to be meaningful:
Body as a Whole: face edema, photosensitivity reaction, shock, asthenia, pain, chills, accidental fall, abdominal pain, allergic reaction, chest pain, accidental injury.
Cardiovascular: angina pectoris, AV block, migraine, syncope, tachycardia, palpitation, hypotension, postural hypotension, myocardial ischemia, cerebralthrombosis, cardiac arrest, heart failure, abnormal electrocardiogram,cardiomyopathy.
Digestive: vomiting, glossitis, colitis, dysphagia, gastritis, gastroenteritis,esophagitis, stomatitis, dry mouth, liver function tests abnormal, rectalhemorrhage, gingivitis.
Hemic and Lymphatic: anemia and leukopenia.
Metabolic and Nutritional: thirst, edema, gout, unstable diabetes,hyperglycemia, peripheral edema, hyperuricemia, hypoglycemic reaction,hypernatremia.
Musculoskeletal: arthritis, arthrosis, myalgia, tendon rupture, tenosynovitis, bone pain, myasthenia, synovitis.
Nervous: ataxia, hypertonia, neuralgia, neuropathy, paresthesia, tremor,vertigo, depression, insomnia, somnolence, abnormal dreams, reflexes decreased, hypesthesia.
Respiratory: asthma, dyspnea, laryngitis, pharyngitis, sinusitis, bronchitis, sputum increased, cough increased.
Skin and Appendages: urticaria, herpes simplex, pruritus, sweating, skin ulcer, contact dermatitis, exfoliative dermatitis.
Special Senses: sudden decrease or loss of hearing, mydriasis,conjunctivitis, photophobia, tinnitus, eye pain, ear pain, eye hemorrhage,cataract, dry eyes.
Urogenital: cystitis, nocturia, urinary frequency, breast enlargement, urinary incontinence, abnormal ejaculation, genital edema and anorgasmia.
Analysis of the safety database from controlled clinical trials showed no apparent difference in adverse reactions in patients taking VIAGRA with and without anti-hypertensive medication. This analysis was performed retrospectively, and was not powered to detect any pre-specified difference in adverse reactions.

Postmarketing Experience

The following adverse reactions have been identified during post approval use of VIAGRA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These events have been chosen for inclusion either due to their seriousness, reporting frequency, lack of clear alternative causation, or a combination of these factors.
Cardiovascular and Cerebrovascular
Serious cardiovascular, cerebrovascular, and vascular events, includingmyocardial infarction, sudden cardiac death, ventricular arrhythmia, cerebrovascular hemorrhage, transient ischemic attack, hypertension,subarachnoid and intracerebral hemorrhages, and pulmonary hemorrhage have been reported post-marketing in temporal association with the use of VIAGRA. Most, but not all, of these patients had preexisting cardiovascular risk factors. Many of these events were reported to occur during or shortly after sexual activity, and a few were reported to occur shortly after the use of VIAGRA without sexual activity. Others were reported to have occurred hours to days after the use of VIAGRA and sexual activity. It is not possible to determine whether these events are related directly to VIAGRA, to sexual activity, to the patient's underlying cardiovascular disease, to a combination of these factors, or to other factors [see WARNINGS AND PRECAUTIONSand PATIENT INFORMATION].
Hemic and Lymphatic: vaso-occlusive crisis: In a small, prematurely terminated study of REVATIO (sildenafil) in patients with pulmonary arterial hypertension (PAH) secondary to sickle cell disease, vaso-occlusive crises requiring hospitalization were more commonly reported in patients who received sildenafil than in those randomized to placebo. The clinical relevance of this finding to men treated with VIAGRA for ED is not known.
Nervous: seizure, seizure recurrence, anxiety, and transient global amnesia.
Respiratory: epistaxis
Special Senses
Hearing: Cases of sudden decrease or loss of hearing have been reported postmarketing in temporal association with the use of PDE5 inhibitors, including VIAGRA. In some of the cases, medical conditions and other factors were reported that may have also played a role in the otologic adverse events. In many cases, medical follow-up information was limited. It is not possible to determine whether these reported events are related directly to the use of VIAGRA, to the patient's underlying risk factors for hearing loss, a combination of these factors, or to other factors [see WARNINGS ANDPRECAUTIONS and PATIENT INFORMATION].
Ocular: diplopia, temporary vision loss/decreased vision, ocular redness or bloodshot appearance, ocular burning, ocular swelling/pressure, increasedintraocular pressure, retinal edema, retinal vascular disease or bleeding, andvitreous traction/detachment.
Non-arteritic anterior ischemic optic neuropathy (NAION), a cause of decreased vision including permanent loss of vision, has been reported rarely post-marketing in temporal association with the use of phosphodiesterase type 5 (PDE5) inhibitors, including VIAGRA. Most, but not all, of these patients had underlying anatomic or vascular risk factors for developing NAION, including but not necessarily limited to: low cup to discratio (“crowded disc”), age over 50, diabetes, hypertension, coronary artery disease, hyperlipidemia and smoking. It is not possible to determine whether these events are related directly to the use of PDE5 inhibitors, to the patient's underlying vascular risk factors or anatomical defects, to a combination of these factors, or to other factors [see WARNINGS ANDPRECAUTIONS and PATIENT INFORMATION].
Urogenital: prolonged erection, priapism [see WARNINGS ANDPRECAUTIONS and PATIENT INFORMATION], and hematuria.
Read the Viagra (sildenafil citrate) Side Effects Center for a complete guide to possible side effects