In Part 4b and in following articles in this series about Vitamins, Minerals, and Nutritional Supplements, we will explore dietary supplements used less often by athletes to improve performance. In addition, many non-athletes use these as well.
‘Buyer Beware’ Information about Supplementation
Most supplements are not tested adequately for efficacy, purity, or safety.
Be careful of misleading product information.
‘Natural’ does not mean safe!
‘More’ is seldom better!
Nothing replaces a well-balanced diet that includes a variety of high-quality foods with plenty of nutrients.
Athletes, and others, use supplements at their own risk!
Claims: Garlic is frequently used to reduce hypertension (high blood pressure) and to prevent coronary artery disease by improving lipid (fat) profiles. Other uses include the stimulation of the immune system and treatment for diabetes, reduction and prevention of colds and flu, and of a decline of stress and fatigue.
Mechanism: In hypertension patients, garlic may cause smooth muscle relaxation and vasodilation (dilation of blood vessels, especially the arteries) by stimulating production of endothelial-derived (A thin layer of flat epithelial cells that lines serous (containing serum) cavities, lymph vessels, and blood vessels) relaxation factor. Lipid profiles improve secondary to HMG-CoA reductase inhibitor (statins) activity. Garlic may stimulate humoral (of or relating to bodily fluids) and cellular immunity. Garlic produces a chemical called allicin. This is what seems to make garlic work for certain conditions. Allicin also makes garlic smell. Some products are made “odorless” by aging the garlic, but this process can also make the garlic less effective. It is a good idea to look for supplements that are coated (enteric coating) so they will dissolve in the intestine and not in the stomach.
Efficacy: Garlic is possibly effective in the treatment of hyperlipidemia (an excess quantity of lipid in the blood) hypertension, but evidence is inconclusive. There isn’t enough information to know if garlic is effective for the other conditions people use it for, including: treating a special condition involving high cholesterol in people with HIV/AIDS, earaches, arthritis, allergies, colds, flu, traveler’s diarrhea, and others.
“Hardening of the arteries” (atherosclerosis): As people age, their arteries tend to lose their ability to stretch and flex with age. Garlic seems to reduce this effect.
Colon cancer, rectal cancer, and stomach cancer: Eating garlic seems to reduce the risk of developing these cancers. However, garlic supplements do not seem to offer the same benefit.
Tick bites: Scientists have compared the number of tick bites in people who take high doses of garlic compared to people who do not take garlic. High doses of dietary garlic, over about a five-month period, seem to reduce the number of tick bites.
Fungal infections of the skin (including ringworm, jock itch and athlete’s foot): Ringworm and jock itch respond to treatment with a garlic gel containing 0.6% ajoene (a chemical in garlic) that is applied to the skin. A garlic gel with a higher concentration of ajoene (1%) is needed to be effective against athlete’s foot. In fact, garlic gel with 1% ajoene seems to be about as effective against athlete’s foot as the medicine Lamisil.
Side Effects: Garlic is safe for most people. Garlic can cause bad breath, a burning sensation in the mouth or stomach, heartburn, gas, nausea, vomiting, body odor, and diarrhea. These side effects are often worse with raw garlic. When used on the skin as a thick paste, garlic can cause damage to the skin that is similar to a burn. These are more common with higher doses and with raw garlic.
Dosage: In clinical trials for hyperlipidemia and hypertension, 600-1200 mg/day divided in three doses. Fresh garlic: 5 g/day (about 1 clove) may be used.
Claims: There are many uses associated with gingko biloba: to improve cognitive function in dementia, including Alzheimer’s disease: to treat vascular insufficiency (central and peripheral), dysmenorrhea, and acute mountain sickness; and to improve sleep in depression patients.
Mechanism: Gingko biloba is a free radical scavenger and inhibitor of monoamine oxidase (found in the outer membrane of mitochondria that degrade biogenic amines and are thus responsible for the destruction of transmitter substances at neuronal synapses). MAO inhibitors are often used in clinical depression to block such destruction.
Basic and clinical studies, conducted both in vitro and in vivo, support these beneficial neuroprotective effects of EGb 761. EGb 761 has several major actions; it enhances cognition, improves blood rheology (the branch of physics that studies the deformation and flow of matter and tissue metabolism, and opposes the detrimental effects of ischæmia).
Several mechanisms of action are useful in explaining how EGb 761 benefits patients with AD and other age-related, neurodegenerative disorders. In animals, EGb 761 possesses antioxidant and free radical-scavenging activities. It reverses age-related losses in brain alpha 1-adrenergic, 5-HT1A and muscarinic receptors, protects against ischæmic neuronal death (In medicine, ischæmia is a restriction in blood supply to tissues, causing a shortage of oxygen and glucose needed for cellular metabolism. Ischæmia is generally caused by problems with blood vessels, with resultant damage to or dysfunction of tissue. It also means local anemia in a given part of a body sometimes resulting from congestion, preserves the function of the hippocampal mossy fiber system (memory processing), increases hippocampal high-affinity choline uptake, inhibits the down-regulation of hippocampal glucocorticoid receptors, enhances neuronal plasticity, and counteracts the cognitive deficits that follow stress or traumatic brain injury (this includes MTBI, a possible problem with concussions). Identified chemical constituents of EGb 761 have been associated with certain actions. Both flavonoid and ginkgolide constituents are involved in the free radical-scavenging and antioxidant effects of EGb 761 which decrease tissue levels of reactive oxygen species (ROS) and inhibit membrane lipid peroxidation.
Regarding EGb 761-induced regulation of cerebral glucose utilization, bilobalide increases the respiratory control ratio of mitochondria by protecting against uncoupling of oxidative phosphorylation, thereby increasing ATP levels, a result that is supported by the finding that bilobalide increases the expression of the mitochondrial DNA-encoded COX III subunit of cytochrome oxidase. With regard to its “anti-stress” effect, EGb 761 acts via its ginkgolide constituents to decrease the expression of the peripheral benzodiazepine receptor (PBR) of the adrenal cortex.
Efficacy: According to the Mayo Clinic, the most promising clinical results right now are in the areas of claudication symptoms (leg pain which results from clogged arteries) and multi-infarct dementia (localized necrosis resulting from obstruction of the blood supply and early-stage Alzheimer’s disease leads to dementia).
The effects of EGb 761 on the central nervous system (CNS) underlie one of its major therapeutic indications; (i.e., individuals suffering from deteriorating cerebral mechanisms related to age-associated impairments of memory, attention and other cognitive functions).
EGb 761 is currently used as symptomatic treatment for cerebral insufficiency that occurs during normal ageing or which may be due to degenerative dementia, vascular dementia (caused by blood vessel problems) or mixed forms of both, and for neurosensory disturbances. Depressive symptoms of patients with Alzheimer’s disease (AD) and aged non-Alzheimer patients may also respond to treatment with EGb 761 since this extract has an “anti-stress” effect.
Basic and clinical studies, conducted both in vitro and in vivo, support these beneficial neuroprotective effects of EGb 761. EGb 761 has several major actions; it enhances cognition, improves blood rheology (the branch of physics that studies the deformation and flow of matter and tissue metabolism, and opposes the detrimental effects of ischæmia).
Good results have been seen for dietary supplementation of gingko biloba and what’s being called “cerebral insufficiency” which includes poor concentration, absentmindedness, confusion, decreased physical performance, fatigue, headache, dizziness, depression, and anxiety.
According to studies done for the U.S. military by the National Academy of Sciences, this dietary supplement does pretty well. However, there are a few concerns of which to be aware. Their review shows that in younger and healthy subjects, high acute dosing may enhance mental performance for short periods. Longer dosing for the same purpose still requires additional research.
The report also discussed benefits that may be seen in the treatment of cardiovascular disease by reducing nanoplaque formation in high-risk cardiovascular patients. There are also benefits to liver function as reported through animal models because of the anti-inflammatory and antioxidant properties.
Side effects of ginkgo biloba may include headache, nausea, gastrointestinal upset, diarrhea, dizziness, or allergic skin reactions. More severe allergic reactions have occasionally been reported.
There are some data to suggest that ginkgo biloba can increase bleeding risk, so people who take anticoagulant drugs, have bleeding disorders, or have scheduled surgery or dental procedures should use caution and talk to a health care provider if using ginkgo.
Fresh (raw) ginkgo seeds contain large amounts of a chemical called ginkgotoxin, which can cause serious adverse reactions—even seizures and death. Roasted seeds can also be dangerous. Products made from standardized ginkgo leaf extracts only, contain little ginkgotoxin and appear to be safe when used orally and appropriately. Stay away from gingko biloba seeds!
Tell all your health care providers about any complementary health practices you use. Give them a full picture of what you do to manage your health. This will help ensure coordinated and safe care. For tips about talking with your health care providers about complementary and alternative medicine, see NCCAM’s Time to Talk campaign.
Dosage: Traditional recommendations include ginkgo products containing 24% flavoglycosides (also called flavone glycosides or flavones) and 6% terpenes: 80-240 milligrams of a 50:1 standardized leaf extract daily, or 3-6 milliliters of a 40 milligram per milliliter liquid extract in 2-3 divided doses, or 30-40 milligrams of extract in a tea bag, prepared as a tea, for at least 4-6 weeks. There is a lack of evidence in support of the clinical benefit of small concentrations of ginkgo found in fortified foods. All doses above are oral unless otherwise stated. Beneficial effects may take 4-6 weeks to appear. Ginkgo seeds are potentially toxic and should be avoided. The intravenous ginkgo product Tebonin®, which was available in Germany, was removed from the German market due to significant adverse effects.
40-240 milligrams of extract, tincture, or powder has been taken by mouth daily, divided into two or three doses. Beneficial effects may take 4-6 weeks to appear. Patients have also been treated with intravenous ginkgo preparations: 0.7mg of intravenous extract per minute for 120 minutes, or 100mg of ginkgo in 500 cubic centimeters of normal saline, administered twice daily. Also, 20 milliliters of ginkgo in 250 milliliters of normal saline daily for four weeks and 200 milligrams of EGb 761 infusion for 10 days, followed by a twice-daily oral dose of 80 milligrams for 12 weeks.
Substantial evidence suggests that the accumulation of beta-amyloid derived peptides, and to a lesser extent free radicals, may contribute to the aetiology and/or progression of Alzheimer’s disease (AD). Ginkgo biloba extract (EGb 761) is a well-defined plant extract containing two major groups of constituents, i.e. flavonoids and terpenoids. It is viewed as a polyvalent agent with a possible therapeutic use in the treatment of neurodegenerative diseases of multifactorial origin, e.g. AD, Pick’s, etc.
Melatonin: Melatonin is a hormone secreted by the pineal gland in the brain. It helps regulate other hormones and maintains the body’s circadian rhythm. The circadian rhythm is an internal 24-hour “clock” that plays a critical role in when we fall asleep and when we wake up. When it is dark, your body produces more melatonin; when it is light, the production of melatonin drops. Being exposed to bright lights in the evening or too little light during the day can disrupt the body’s normal melatonin cycles. For example, jet lag, shift work, and poor vision can disrupt melatonin cycles.
Melatonin also helps control the timing and release of female reproductive hormones. It helps determine when a woman starts to menstruate, the frequency and duration of menstrual cycles, and when a woman stops menstruating (menopause).
Some researchers also believe that melatonin levels may be related to aging. For example, young children have the highest levels of nighttime melatonin. Researchers believe these levels drop as we age. Some people think lower levels of melatonin may explain why some older adults have sleep problems and tend to go to bed and wake up earlier than when they were younger. However, newer research calls this theory into question.
Melatonin has strong antioxidant effects. Preliminary evidence suggests that it may help strengthen the immune system.
Insomnia: Studies suggest that melatonin supplements may help people with disrupted circadian rhythms (such as people with jet lag or those who work the night shift) and those with low melatonin levels (such as some seniors and people with schizophrenia) to sleep better. A review of clinical studies suggests that melatonin supplements may help prevent jet lag, particularly in people who cross five or more time zones.
A few clinical studies suggest that when taken for short periods of time (days to weeks) melatonin is more effective than a placebo in reducing the time it takes to fall asleep, increasing the number of sleeping hours, and boosting daytime alertness. It’s not clear how well melatonin works, however — some studies suggest that it only reduces the amount of time to fall asleep by a few minutes.
Several human studies have measured the effects of melatonin supplements on sleep in healthy people. A wide range of doses has been used, often taken by mouth 30 – 60 minutes prior to sleep time. Results have been mixed. Some evidence suggests that melatonin may work best for people over 55 who have insomnia. One study of 334 people aged 55 and older found that sustained-release melatonin seemed to help people fall asleep faster, sleep better, be more alert in the morning, and improve quality of life in people with primary insomnia.
Menopause: Melatonin supplements may help with sleep problems associated with menopause. However, it does not appear to relieve other symptoms of menopause, such as hot flashes. Peri- or postmenopausal women who use melatonin supplements should do so only for a short period of time since long-term effects are not known.
Benzodiazepine Withdrawal: Some clinical research has found that melatonin may help elderly people with insomnia who are tapering off or stopping benzodiazepines such as diazepam (Valium), alprazolam (Xanax), or lorazepam (Ativan). Taking controlled-release melatonin improved sleep quality in those stopping benzodiazepine use. More study is needed, and one should never combine melatonin with sedative medications unless you are under the strict supervision of a health care provider.
Breast Cancer: Several studies suggest that low melatonin levels may be associated with breast cancer risk. For example, women with breast cancer tend to have lower levels of melatonin than those without the disease. Laboratory experiments have found that low levels of melatonin stimulate the growth of certain types of breast cancer cells, while adding melatonin to these cells slows their growth. Preliminary evidence also suggests that melatonin may strengthen the effects of some chemotherapy drugs used to treat breast cancer. In a study that included a small number of women with breast cancer, melatonin (given 7 days before beginning chemotherapy) prevented the lowering of platelets in the blood. This is a common complication of chemotherapy that can lead to bleeding.
In another small study of women who were taking tamoxifen for breast cancer but seeing no improvement, adding melatonin caused tumors to modestly shrink in more than 28% of the women. Women with breast cancer should ask their doctors before taking melatonin.
Prostate Cancer: Studies show that men with prostate cancer have lower melatonin levels than men without the disease. In test tube studies, melatonin blocks the growth of prostate cancer cells. In one small-scale study, melatonin — combined with conventional medical treatment — improved survival rates in 9 out of 14 men with metastatic prostate cancer. Interestingly, since meditation may cause melatonin levels to rise it appears to be a valuable addition to the treatment of prostate cancer. More research is needed before doctors can make recommendations in this area. Men with prostate cancer should talk to their doctor before taking medication.
Attention Deficit Hyperactivity Disorder (ADHD) and Autism: Some evidence suggests that melatonin may help promote sleep in children with ADHD or autism, although it does not seem to improve the behavioral symptoms of ADHD or autism.
Fibromyalgia: A randomized, placebo-controlled study found that people with fibromyalgia experienced a significant reduction in their symptoms when they took a melatonin supplement either alone or in conjunction with fluoxetine (Prozac).
Sunburn — A few small clinical studies suggest that gels, lotions, or ointments containing melatonin may protect against sunburn and other skin damage. Studies examined using melatonin alone or combined with topical vitamin E prior to UV light exposure from the sun.
Irritable Bowel Syndrome — Some preliminary studies suggest that people with IBS who take melatonin reduce some symptoms of IBS, such as abdominal pain. But results are mixed as to whether melatonin may help improve other symptoms, such as bloating and frequency of bowel movements.
Epilepsy — Some studies suggest melatonin may reduce the frequency and duration of seizures in children with epilepsy. But other studies suggest melatonin may increase the frequency of seizures. Do not take melatonin for epilepsy or give it to a child without talking to your doctor first.
Sarcoidosis — Some researchers suggest that melatonin may be effective in the treatment of pulmonary sarcoidosis. In pulmonary sarcoidosis, small patches of inflamed cells can appear on the lungs’ small air sacs (alveoli), breathing tubes (bronchioles) or lymph nodes. The lungs can become stiff and may not be able to hold as much air as healthy lungs. In serious cases, sarcoidosis can cause scar tissue in the lungs, which can affect the lungs’ ability to move oxygen into the bloodstream. Talk to your doctor.
Efficacy: Older people typically exhibit poor sleep efficiency and reduced nocturnal plasma melatonin levels. The daytime administration of oral melatonin to younger people, in doses that raise their plasma melatonin levels to the nocturnal range, can accelerate sleep onset.
The physiologic melatonin dose (0.3 mg) restored sleep efficiency (P < 0.0001 – very high probability of success), acting principally in the midthird of the night; it also elevated plasma melatonin levels to normal (P < 0.0008 – also quite high probability of success). The pharmacologic dose (3.0 mg), like the lowest dose (0.1 mg), also improved sleep; however, it induced hypothermia (low body temperature) in some and caused plasma melatonin to remain elevated into the daylight hours (early morning sleepiness). Although control subjects (whose sleep was normal), like insomniacs, had low melatonin levels, their sleep was unaffected by any melatonin dose.
Oral administration of melatonin to normal human males increases basal GH (growth hormone) release and GH responsiveness to GHRH (growth hormone releasing hormone) through the same pathways as pyridostigmine, an orally active cholinesterase inhibitor – ‘second-generation’ cholinesterase inhibitors (ChEIs) are donepezil, galantamine and rivastigmine. Therefore it is likely that melatonin plays this facilitatory role at the hypothalamic level by inhibiting endogenous somatostatin release (inhibits the activity of certain pancreatic and gastrointestinal hormones), although with a lower potency than pyridostigmine. The physiological role of melatonin in GH neuroregulation remains to be established.
These medications have proven efficacy in improving cognition, behavior, activities of daily living, and global functioning in mild-to-moderate AD.
Side Effects: The most common melatonin side effects include: daytime sleepiness, dizziness, and headaches. Other, less common melatonin side effects include abdominal discomfort, mild anxiety, irritability, confusion and short-lasting feelings of depression.
In addition, melatonin supplements can interact with various medications, including: Blood-thinning medications (anticoagulants), medications that suppress the immune system (immunosuppressants), diabetes medications, and birth control pills.
Dosage: If you are considering taking melatonin supplements, check with your doctor first — especially if you have any health conditions. The correct dose depends on the intended use. For example, circadian rhythm sleep disorders are often treated with 0.5 milligrams of melatonin a day, while doses of 3 to 5 milligrams a day might be used to treat jet lag or reduce the time it takes to fall asleep. In addition, remember that melatonin is generally recommended only for short-term use — up to two months. Some research indicates that longer term use might be appropriate in certain cases, however.
If you take melatonin, choose commercial supplements produced in a laboratory. Melatonin supplements made from animal sources may contain various contaminants. Do not engage in activities that require alertness — such as driving or operating heavy machinery — for four to five hours after taking melatonin. While this warning is usually greeted with great skepticism, it is vital for safety to follow the dictum faithfully.
Niacin: Niacin is a member of the B family of vitamins (B complex). Niacin is a water-soluble vitamin and excess amounts are excreted through the kidneys. Like the other B vitamins, niacin plays an important role in energy production.
Niacin functions in two important enzyme systems (NAD and NADP) that affect all the tissues of the body. These enzyme systems help transport hydrogen within the cell and make it available for biosynthesis. These two enzymes also function closely with the energy molecule adenosine triphosphate (ATP).
All B vitamins help the body to convert food (carbohydrates) into fuel (glucose), which is used to produce energy. These B vitamins, often referred to as B complex vitamins, also help the body use fats and protein. B complex vitamins are needed for healthy skin, hair, eyes, and liver. They also help the nervous system function properly. Niacin also helps the body make various sex and stress-related hormones in the adrenal glands and other parts of the body. Niacin helps improve circulation. All the B vitamins are water-soluble, meaning that the body does not store them.
Other names: vitamin B3, niacinamide, nicotinamide, nicotinic acid, nicotinic acid amide.
Claims: Nicotinic acid or niacinamide are used to treat and prevent pellagra (a disease caused by niacin deficiency). Niacin is also used to treat elevated cholesterol. In some cases niacin, in conjunction with colestipol (used to lower high cholesterol levels in the blood, and can be as effective as a combination of colestipol and one of the “statin” drugs (e.g., lovastatin, pravastatin, or simvastatin) to treat elevated blood cholesterol (hyperlipidemia).
Niacin is also used as an adjunct in peripheral vascular disease/coronary artery disease. It is said to augment energy during exercise. It may decrease pain in osteoarthritis.
Mechanism: Niacin may increase homocysteine levels (homocysteine is a naturally occurring amino acid found in blood plasma, and high levels of homocysteine in the blood are believed to increase the chance of heart disease, stroke, Alzheimer’s disease, and osteoporosis. Homocysteine is thought to irritate the lining of the blood vessels causing them to become scarred, hardened, and narrowed. This increases the work the heart must do, leading to heart disease. High levels of homocysteine also cause increased blood clotting. Blood clots can decrease or block the flow of blood through blood vessels, resulting in strokes and heart attacks. If and how homocysteine directly plays a role in osteoporosis and Alzheimer’s disease is not clear as of 2005.
The level of homocysteine in the blood naturally varies with age, gender, diet, hereditary factors, and general health, but it is estimated that 5-10% of the population has homocysteine levels that are considered high. With the exception of rare individuals who have congenital homocystinuria, people with high blood levels of homocysteine do not have any obvious signs or symptoms. Individuals who increase the folic acid, vitamin B6 and B12 in their diet are expected to see a decrease in blood levels of homocysteine and as a result decrease their risk of heart disease and stroke. B-complex vitamins such as niacin, are involved in energy production during exercise.
Efficacy: The pharmacokinetics (how pharmaceuticals work in the body), efficacy, and safety of niacin and its various formulations are important to know. Niacin has been used for decades for the treatment of dyslipidemia because of its favorable effects on all lipoprotein parameters. Niacin significantly increases high-density lipoprotein cholesterol (HDL-C) more than any other available agent and reduces total cholesterol, low-density lipoprotein cholesterol (LDL-C), lipoprotein (a), and triglycerides.
Niacin is currently available in immediate-release (IR), sustained-release (SR), and extended-release (ER) formulations that differ in their dissolution, pharmacokinetic, efficacy, and safety profiles.
Side Effects: Important drawbacks to niacin therapy such as cutaneous flushing, associated with IR niacin, and hepatotoxicity (liver toxicity) associated with SR niacin, have historically limited its use. The adverse effect profiles of the different niacin formulations can be explained by differences in their dissolution and absorption rates and metabolic disposition, which result in production of metabolites associated with the respective adverse effects. The ER niacin formulation, with an intermediate dissolution rate between the dissolution rates of IR and SR niacin, demonstrates reduced rates of cutaneous flushing compared with IR niacin and hepatotoxic effects compared with SR niacin.
You can meet all of your body’s needs for B3 through diet. It is rare for anyone in the developed world to have a B3 deficiency. In the United States, alcoholism is the main cause of vitamin B3 deficiency. Symptoms of mild deficiency include indigestion, fatigue, canker sores, vomiting, and depression. Severe deficiency can cause a condition known as pellagra. Pellagra is characterized by cracked, scaly skin, dementia, and diarrhea. It is generally treated with a nutritionally balanced diet and niacin supplements. Niacin deficiency also causes burning in the mouth and a swollen, bright red tongue.
Very high doses of B3, available by prescription, have been studied to prevent or improve symptoms of the following conditions. However, at high doses niacin can be toxic: You can meet all of your body’s needs for B3 through diet. It is rare for anyone in the developed world to have a B3 deficiency. In the United States, alcoholism is the main cause of vitamin B3 deficiency.
Symptoms of mild deficiency include indigestion, fatigue, canker sores, vomiting, and depression. Severe deficiency can cause a condition known as pellagra. Pellagra is characterized by cracked, scaly skin, dementia, and diarrhea. It is generally treated with a nutritionally balanced diet and niacin supplements. Niacin deficiency also causes burning in the mouth and a swollen, bright red tongue.
Very high doses of B3, available by prescription, have been studied to prevent or improve symptoms of the following conditions: high cholesterol, atherosclerosis heart disease, arteriosclerosis, and osteoarthritis.
Other diseases include:
Alzheimer’s disease — Population studies show that people who get higher levels of niacin in their diet have a lower risk of Alzheimer’s disease. No studies have evaluated niacin supplements, however.
Cataracts — One large population study found that people who got a lot of niacin in their diets had a lower risk of developing cataracts.
Skin conditions — Researchers are studying topical forms of niacin as treatments for rosacea, aging, and prevention of skin cancer, although it’s too early to know whether it is effective.
Researchers are also studying the use of vitamin B3 in treating ADHD, migraines, dizziness, depression, motion sickness, and alcohol dependence. But there is no evidence that it helps treat any of these conditions.
However, at high doses niacin can be toxic. You should not take doses higher than the Recommended Daily Allowance except under your doctor’s supervision. You should not take doses higher than the Recommended Daily Allowance (RDA) except under your doctor’s supervision.
Taking too much over-the-counter or prescription niacin can be dangerous. You may have heard that too much niacin can be harmful because of Internet rumors. The rumors falsely state that by taking a large amount of niacin, people can flush the chemicals that show they’ve used marijuana out of their bodies before they take a drug test. No studies have shown that niacin can do this, and this can be very dangerous because it may lead to niacin overdose.
Niacin overdose symptoms include: severe skin flushing combined with dizziness, rapid heartbeat, itching, nausea and vomiting, abdominal pain, diarrhea, and severe liver damage (hepatoxicity)
If you’re concerned about a potential niacin overdose, talk to your doctor to make sure you’re taking the correct amount. If you think you may have overdosed, seek medical attention immediately.
Because of the potential for side effects and interactions with medications, you should take dietary supplements only under the supervision of a knowledgeable health care provider.
High doses (50 mg or more) of niacin can cause side effects. The most common side effect is called “niacin flush,” which is a burning, tingling sensation in the face and chest, and red or flushed skin. Taking an aspirin 30 minutes prior to the niacin may help reduce this symptom. At the very high doses used to lower cholesterol and treat other conditions, liver damage and stomach ulcers can occur. Your health care provider will regularly check your liver function through a blood test.
People with a history of liver disease, kidney disease, or stomach ulcers should not take niacin supplements. Those with diabetes or gallbladder disease should do so only under the close supervision of their doctor.
Stop taking niacin or niacinamide at least two weeks before a scheduled surgery.
Niacin and niacinamide may make allergies worse by increasing histamine.
People with low blood pressure should not take niacin or niacinamide because they may cause a dangerous drop in blood pressure. Do not take niacin if you have a history of gout.
People with coronary artery disease or unstable angina should not take niacin without their doctor’s supervision, as large doses can raise the risk of heart rhythm problems.
Taking any one of the B vitamins for a long period of time can result in an imbalance of other important B vitamins. For this reason, you may want to take a B complex vitamin, which includes all the B vitamins.
If you are currently taking any of the following medications, you should not use niacin without first talking to your health care provider.
Antibiotics, Tetracycline — Niacin should not be taken at the same time as the antibiotic tetracycline because it interferes with the absorption and effectiveness of this medication. All vitamin B complex supplements act in this way and should be taken at different times from tetracycline.
Aspirin — Taking aspirin before taking niacin may reduce flushing from niacin, but take it only under your doctor’s supervision.
Anti-seizure Medications — Phenytoin (Dilantin) and valproic acid (Depakote) may cause niacin deficiency in some people. Taking niacin with carbamazepine (Tegretol) or mysoline (Primidone) may increase levels of these medications in the body.
Anticoagulants (blood thinners) — Niacin may make the effects of these medications stronger, increasing the risk of bleeding.
Blood Pressure Medications, Alpha-blockers — Niacin can make the effects of medications taken to lower blood pressure stronger, leading to the risk of low blood pressure.
Cholesterol-lowering Medications — Niacin binds the cholesterol lowering medications known as bile-acid sequestrants and may make them less effective. For this reason, niacin and these medications should be taken at different times of the day. Bile-acid sequestrants include colestipol (Colestid), colesevelam (Welchol), and cholestyramine (Questran).
Statins — Some scientific evidence suggests that taking niacin with simvastatin (Zocor) appears to slow down the progression of heart disease. However, the combination may also increase the likelihood for serious side effects, such as muscle inflammation or liver damage.
Diabetes Medications — Niacin may increase blood sugar levels. People taking insulin, metformin (Glucophage), glyburide (Dibeta, Micronase), glipizide (Glucotrol), or other medications used to treat high blood glucose levels should monitor their blood sugar levels closely when taking niacin supplements.
Isoniazid (INH) — INH, a medication used to treat tuberculosis, may cause a niacin deficiency.
Nicotine Patches — Using nicotine patches with niacin may worsen or increase the risk of flushing associated with niacin.
These medications may lower levels of niacin in the body:
|Chloramphenicol (Chloromycetin)||Levodopa and carbidopa|
|Cycloserine (Seromycin)||Mercaptopurine (Purinethol)|
Table 1. Niacin-level lowering medications.
The daily recommended dietary allowances (RDAs) of niacin are:
Infants 0-6 months, 2 mg
Children 9-13 years, 12 mg
Infants 7-12 months, 4 mg
Men 14 years and older, 16 mg
Children 1-3 years, 6 mg
Women 14 years and older, 14 mg
Children 4-8 years, 8 mg
Pregnant women, 18 mg
Lactating women, 17 mg
Table 1. RDAs for niacin.
The maximum daily dose of niacin is:
|Children 1-3 years, 10 mg||Adults, including Pregnant and Lactating women, 14-18 years, 30 mg|
|Children 4-8 years, 15 mg||Adults, including pregnant and breast-feeding women, older than 18 years, 35 mg|
|Children 9-13 years, 20 mg||For patients with medical disorders, the amount prescribed by your doctor vary according to disorder, age, pharmacokinetics, condition of the patient, and possible drug interactions (which there are some for niacin).|
Table 2. Maximum Daily Dose of niacin.
Resveratrol: Certain metabolic diseases, including type 2 diabetes and heart disease, tend to strike as we age. In animal studies, severely restricting calories can help prevent some of these diseases. Over a decade ago, researchers found that resveratrol can mimic calorie restriction in some ways and extend the lifespans of yeast, worms, flies and fish.
Claims: Among resveratrol’s most intriguing aspects is how it functions as an antioxidant. Oxidation is a natural chemical process in living tissues that results in a transfer of electrons. When this happens, groups of atoms are formed called “free radicals” that can cause cell damage which in turn provides a pathway for diseases. Antioxidants, however, suppress free radicals. It is not so easy to say resveratrol is the main factor. It is one piece of the overall puzzle that reduces the free radicals.
An important well-run study also reveals that resveratrol’s contribution to good health promises to be widespread. Various clinical trials, for example, indicate that this polyphenol — an antibiotic substance produced by plants as a defense against microorganisms — prevents the growth of some cancers in mice, inhibits enzymes that cause inflammation, shrinks tumors and increases blood flow, thus reducing cardiovascular diseases. In many cases, it also extends the life of obese animals. Some evidence also shows that resveratrol could one day be used to help regulate insulin sensitivity in diabetic patients.
One of the reasons that people question the value of resveratrol in humans is that few human studies have been done.
Mechanisms: Resveratrol affects the activity of enzymes called sirtuins. Sirtuins control several biological pathways and are known to be involved in the aging process.
Resveratrol is only one of many natural and synthetic sirtuin-activating compounds (STACs) now known.
STACs ultimately increase the activity of mitochondria, the organelles that produce the cell’s energy. Some believe that this may be how STACs affect age-related diseases.
Studies found no evidence for the involvement of other biological pathways that were previously linked to the effects of STACs. These results suggest that resveratrol and other STACs act, at least in part, through direct interactions with SIRT1 and its substrates. Further research will be needed to understand which of these pathways are responsible for the effects of STACs in the body.
A recent study (2012) uncovered intermediate steps between resveratrol and sirtuins. A key step in this pathway is an enzyme called AMPK, which regulates energy levels in the cell. However, the link between resveratrol and AMPK has been a mystery.
Researchers were able to identify an enzyme called PDE4 in the skeletal muscle as the principal target for the health benefits of resveratrol. Resveratrol inhibits PDE4, which raises levels of an important cell signaling molecule called cAMP. Levels of cAMP normally rise when cells get the signal that blood glucose levels are low. Resveratrol thus activates one of the same biochemical pathways as a low-calorie diet. This pathway ultimately activates AMPK and sirtuins.
As this study shows, the biochemical pathways affected by resveratrol are complex and far-reaching. As a natural product, resveratrol likely has additional targets, which could lead to side effects. These findings may now help researchers design effective drugs without those potential problems.
Efficacy: Resveratrol has been shown in animal and laboratory studies to exhibit antioxidant, anticancer, antiproliferative, antifungal, antiviral, and antibacterial effects. However, data in humans is lacking.
At this time, there is a lack of high quality human trials available supporting the efficacy of resveratrol for any indication. However, there are several observational studies that correlate the consumption of wine with a decrease in cancer and/or cardiovascular disease risk. There are multiple possible contributing factors to these conditions, and studies of resveratrol are difficult to design and implement. Too much alcohol intake can be dangerous. Further research is needed before a firm recommendation can be made.
The effects of resveratrol cannot be adequately assessed from trials using foods, wine, or combination products containing resveratrol and other substances. Well-designed clinical trials of resveratrol alone are needed before a recommendation can be made.
The below uses are based on tradition, scientific theories, or limited research. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider. There may be other proposed uses that are not listed below:
Age-related macular degeneration, allergy, Alzheimer’s disease, amyloidosis, amyotrophic lateral sclerosis, antifungal, anti-inflammatory, antimicrobial, antioxidant, antiplatelet, anti-tumor agent, antiviral, atherosclerosis, bone density, cancer prevention, cerebral ischemia, chemoprotectant, chronic obstructive pulmonary disease (COPD), cognitive disorders, cosmetic, degenerative diseases, diabetic neuropathy, diabetic wound healing, edema, Epstein-Barr virus, hearing loss, infection, herpes simplex virus types 1 and 2, HIV, hormonal imbalances, hypercholesterolemia, immunomodulator, influenza, ischemia-reperfusion injury prevention, leukemia, medulloblastoma, menopausal symptoms, multiple sclerosis, nephrotoxicity, neuroblastoma, neuropathy, neuroprotection, pain, pancreatitis, Parkinson’s disease, premature aging, renal impairment (protection), rheumatoid arthritis, seizure, skin disorders, spinal cord injury, stroke, vascular diseases, vasorelaxant, wound healing.
Side Effects: When taken in excess dosage (1500 mg and above), resveratrol can lead to overdose symptoms. The probable resveratrol supplements side effects are abdominal cramps, loose motion, joint pain, blood thinning, anemia and hand tingling.
Allergies: Avoid in individuals with a known allergy/hypersensitivity to resveratrol, grapes, and red wine or red wine polyphenols.
Allergic contact dermatitis from pentylene glycol in an emollient cream, with possible co-sensitization to resveratrol has been reported.
Side Effects and Warnings: Limited data in humans reveals that resveratrol seems quite safe. It is usually found as a component in food and beverages.
There is limited long-term information regarding adverse effects associated with resveratrol supplements alone. The American Heart Association recommends limited consumption. Consumption of large quantities of red wine as a source of resveratrol is considered unsafe due to the alcohol content. Consuming large amounts of alcohol increases the risk of alcoholism, high blood pressure, obesity, stroke, breast cancer, suicide, and accidents. Drinking large quantities of red wine may also have adverse effects on the liver. Preliminary evidence suggests that resveratrol may weakly inhibit the way that the liver breaks down certain drugs, herbs, and supplements. Avoid red wine consumption in patients with a history of alcoholism.
Use cautiously in patients on anticoagulant/antiplatelet (blood thinning) agents due to the potential for increased risk of bleeding.
Patients on blood pressure medications should take high amounts of resveratrol with caution.
Pregnancy and Breastfeeding: According to the American College of Obstetricians and Gynecologists, red wine consumption is not recommended in pregnant women, as alcohol may affect the fetus and can lead to life-threatening damage.
Interactions with Drugs: Based on preliminary laboratory study, resveratrol may have additive effects when taken with antifungals, such as nystatin. There may be a protective effect of trans-resveratrol on gentamicin-induced kidney toxicity.
Laboratory study suggests that resveratrol has anti-aggregating and antithrombin activity and may have additive effects when taken with other drugs with the same actions. Use of resveratrol with antiplatelet drugs like clodipogrel (Plavix®), dipyridamole (Persantine®), non-steroidal anti-inflammatory drugs (NSAIDs), and aspirin or anticoagulant drugs like warfarin (Coumadin®) could cause increased risk of bleeding.
Resveratrol may increase the effects of some antivirals, including antiretroviral HIV medications.
Based on laboratory and animal study, the use of resveratrol with antihypertensive/cardiovascular drugs may result in additive effects.
Based on laboratory study, resveratrol may sensitize or enhance the efficacy of anticancer drugs, such as paclitaxel or actinomycin D.
Cholesterol levels have been lowered in rats, although the clinical significance is unknown in humans. In theory, resveratrol could increase the effects of cholesterol-lowering drugs such as HMG-CoA reductase inhibitors (“statins”) or bile acid sequestering agents (cholestyramine).
Based on preliminary data, resveratrol may enhance the immune suppression caused by cyclosporine A.
Drinking large quantities of red wine, which contains resveratrol, may have adverse effects on the liver. Preliminary evidence suggests that resveratrol may weakly inhibit the way that the liver breaks down certain drugs, herbs, and supplements.
Based on resveratrol’s chemical structure, which is similar to that of the synthetic estrogen agonist diethylstilbestrol, resveratrol may function as an estrogen agonist (activation) and exhibit an additive effect when taken in conjunction with estradiol. However, limited laboratory study has shown resveratrol acting as an estrogen antagonist (blocking activation). Resveratrol may have the potential to act as both an estrogen agonist and antagonist depending on a variety of factors.
Based on preliminary study, resveratrol may interact with MAOIs such as phenelzine (Nardil®) and tranylcypromine (Parnate®). This effect has not been confirmed in humans.
Resveratrol may also interact with anti-inflammatory agents, vasorelaxants, neurologic agents, immune enhancing agents or agents that alter blood sugar levels.
Dosage: It is clear that resveratrol protects human health through chemoprevention to cardioprotection. Resveratrol provides protection against cancer, cardiovascular diseases, ageing related diseases and also possess chemoprotective, neuroprotective, anti-inflammatory properties. In case of myocardial injury and ageing related diseases, resveratrol protects cells from apoptosis thereby working as an anti-apoptotic agent whereas in cancer prevention, resveratrol kills the cancer cell by inducing apoptosis, thus working as a pro-apoptotic agent. So resveratrol can function both as pro-apoptotic and anti-apoptotic agents.
There are numerous plant-derived natural components, vitamins and minerals whose daily allowance requirement are safe and promote good health when taken at a low dose. When the same substances are taken at a high dose, they become toxic and produce adverse effects to the cells at the subcellular levels. Similarly, resveratrol is good for health but the health benefit of resveratrol is dose-dependent. Low doses resveratrol protect health from different types of diseases, while high doses resveratrol can be detrimental for health. However, high dose resveratrol may be required in pathological conditions such as destroying cancer cells.
Adverse effects of resveratrol have not been reported, but only a small number of studies have been done on humans. In one human study, a 5 mg dose was used safely, and animal studies have used doses up to 300 mg per kg body weight for four weeks with no adverse effects. The Linus Pauling Institute cautions that resveratrol exerts estrogen-like effects and may interact with prescription drugs.
There is no specific dose of resveratrol that is considered suitable for a person. With reference to a clinical trial conducted on mice, resveratrol is found to be most effective when given in 5 mg/kg of body weight. Considering this, medical researchers come to the conclusion that this same resveratrol concentration is also ideal for humans. Hence, considering the average body weight of adult men and women, the recommended resveratrol dosage is 200 mg to 400 mg per person per day. Taking more than 1500 mg without medical supervision is not at all recommended.
One prime reason for huge popularity of resveratrol supplements is positive weight loss effects, without adverse reactions. While using this antioxidant supplement for losing weight, the ideal dose varies with respect to body weight of the dieter. It is suggested that a dose of about 300 mg is good for a person weighing 150 pounds. Likewise, resveratrol dosage will be higher than 300 mg for a 300 pound man or woman. Between 100-500 mg concentration is considered low dosage, while medium dosage refers to intake of 500-1500 mg per day. High dosage is >1500 mg/day.
When taken in excess dosage (>1500 mg), resveratrol can lead to overdose symptoms. The probable resveratrol supplements side effects are abdominal cramps, loose motion, joint pain, blood thinning, anemia and hand tingling. On a concluding note, consulting a trusted doctor about the appropriate dosage intake is crucial while taking any type of antioxidant formulations, including resveratrol-based products. So, in order to minimize the risk of resveratrol side effects, do not self-administer this therapeutic supplement.
Consult your doctor about using resveratrol to treat a medical condition.
Claims: Saw palmetto (Serenoa repens/Sabal serrulata) is a palm like plant with berries that were a staple food and medicine for the Native Americans of the southeastern United States. In the early 1900s, men used the berries to treat urinary tract problems, and even to increase sperm production and boost libido. Today, the primary use of saw palmetto is to treat benign prostatic hyperplasia (BPH), a noncancerous enlargement of the prostate gland.
Mechanism: Researchers aren’t sure exactly how saw palmetto works, but it contains plant-based chemicals that may be effective for BPH. Researchers think that saw palmetto may affect the level of testosterone in the body, and perhaps reduce the amount of an enzyme that promotes the growth of prostate cells. Saw palmetto is often combined with nettle extract to treat BPH.
Saw palmetto has antiandrogenic effects, (counters the effects of androgens (e.g., testosterone)
Efficacy: Evidence is mixed about whether saw palmetto works to treat BPH. Several studies suggest that the herb is effective for treating symptoms, including too frequent urination, having trouble starting or maintaining urination, and needing to urinate during the night. The urethra, the tube that empties urine from the body, runs through the prostate gland in men; when the prostate gland is enlarged, men may have trouble urinating.
Some studies show that saw palmetto is as effective in treating symptoms as finasteride (Proscar) without side effects, such as loss of libido. Other studies suggest that saw palmetto may actually shrink the size of the prostate gland. Due to the short duration (usually less than 3 months) of these studies, it is not possible to say for sure whether saw palmetto is truly effective for preventing complications of BPH. In fact, a well-conducted study published in the New England Journal of Medicine found that saw palmetto was no better than placebo in relieving the signs and symptoms of BPH (the prostate is a gland about the size of a walnut that is only present in men. It is located just below the bladder and surrounds the urethra, the tube through which urine flows from the bladder and out through the penis). The gland is divided into three zones, peripheral, transitional and central. In Benign Prostatic Hyperplasia (BPH), there is an overgrowth of cells in the central portion of the prostate. This constricts the urethra, reduces the flow of urine and makes it difficult for the patient to empty his bladder. It is important to receive a proper diagnosis of BPH from your health care provider to rule out prostate cancer.
A 72-week double-blind, multicenter placebo-controlled trial to assess the effect of double (640 mg/d) and triple (960 mg/d) the standard dose of saw palmetto extract on BPH symptoms was done. The study included 369 men with moderate LUTS (lower urinary tract symptoms) who had not recently received treatment for BPH. Exclusion criteria included a history of invasive BPH treatment, recent treatment with either an alpha-blocker or a 5-alpha-reductase inhibitor; recent phytotherapy, including saw palmetto; and a history of prostate or bladder cancer. Participants were randomized to receive either saw palmetto extract or an identical-looking placebo gel cap. Doses started at 320 mg/d and were increased to 640 mg/d at 24 weeks and 960 mg/d at 48 weeks.
The primary outcome was the change in the American Urological Association Symptom Index (AUASI) score from baseline to 72 weeks. AUASI, a scale of 0 to 35 in which higher numbers represent increased symptoms. Secondary measures included other symptom scales, peak uroflow, and poststudy satisfaction. The treatment and placebo groups had statistically identical baseline characteristics, and the sample size was large enough to detect clinically significant differences.
The AUASI score decreased by a mean of 2.20 points (95% confidence interval [CI], -3.04 to -0.36) in the group that received saw palmetto and by 2.99 points (95% CI, -3.81 to -2.17) in the placebo group—a mean difference of 0.79 in favor of the placebo group. The proportion of participants achieving a 3-point reduction in AUASI score was statistically similar between the 2 groups. There was no significant dose response difference between the 2 groups, and saw palmetto proved to be no better than placebo for any of the secondary outcomes.
Subgroup analysis did not reveal any results that differed from the main outcomes. The only adverse events that were significantly different between the 2 groups related to physical injury or trauma, which were unlikely to be due to the intervention.
By using the same symptom scoring system (AUASI) as many studies in previous reviews, researchers were able to compare their findings with those of other high-quality studies with similar methodologies and outcome measures. Despite using an even higher dose of the extract, the results of this trial are remarkably consistent with previous conclusions: Saw palmetto is not an effective treatment for symptoms associated with BPH. Moreover, this trial had a broad base of participants similar to the population in a primary care practice, including patients who would typically choose a natural remedy for LUTS.
Side Effects: BPH and problems with sexual function become more and more common as men get older. So it is not surprising that many men with BPH have problems with sexual function as well. These problems include lower sexual desire (libido), ejaculation problems, and erectile dysfunction. It is also well known that some treatments for BPH have an impact on sexual function (e.g., surgery – may men complain that sex problems are much worse), so it is important for you and your partner to understand how these treatments can affect your sexual relationship.
It may take up to a year for sexual function to return to normal after surgery, but the good news is that with time, most men will be able to enjoy sex again. The effect of BPH surgery on sexual function varies depending on the type of procedure. Minimally invasive procedures such as TUMT and TUNA do not appear to have an effect on a man’s ability to withhold urine during erections.
During surgical procedures such as TURP and open surgery, the muscle that normally closes off the entrance to the bladder during ejaculation is cut. This can lead to a condition called retrograde ejaculation, or dry climax. This condition is not harmful to your health. It means that during ejaculation, the sperm do not exit through the penis but instead enter the bladder and are flushed out in the urine. Although this “dry climax” may feel different, most men find they can enjoy sex as much as they did before surgery.
Selective alpha-blockers work by relaxing the smooth muscle in the prostate and the bladder neck. But they may also relax the muscles in the vas deferens, the part of the male reproductive system that helps propel the sperm out into the urethra and penis. This means that ejaculation may occur with little or no semen. As with retrograde ejaculation after surgery, this change in climax is not harmful to your health. Also, this side effect will stop if medication is discontinued. Alpha-blockers do not affect a man’s ability to have erections or achieve orgasm.
The most common side effects of 5-alpha-reductase inhibitors are related to sexual function. The 5-ARIs interfere with the body’s production of dihydrotestosterone, a male hormone. Sexual side effects may include impotence, decreased sexual desire, reduced semen with ejaculation, and other ejaculation problems
The use of herbs is a time honored approach to strengthening the body and treating disease. Herbs, however, can trigger side effects and interact with other herbs, supplements, or medications. For these reasons, you should take herbs with care, under the supervision of a health care provider.
Saw palmetto is generally thought to be safe when used as directed. Side effects are very rare, although mild stomach complaints and minor headaches may occur. In at least one case, significant bleeding during surgery was attributed to saw palmetto. There have been two reports of liver damage and one report of pancreas damage in people who took saw palmetto, but there is not enough information to know if saw palmetto was the actual cause of these effects.
Do not self-treat for BPH with saw palmetto; see your health care provider for a proper diagnosis to rule out prostate cancer.
Saw palmetto may have effects similar to some hormones, and should not be used in pregnant or nursing women, or women who have had or are at risk for hormone related cancers.
Saw palmetto may interfere with the absorption of iron.
Possible interactions: Finasteride (Proscar) — Because saw palmetto may work similarly to finasteride (Proscar), you should not use this herb in combination with finasteride or other medications used to treat BPH unless directed to by your physician, antiplatelet and anticoagulant drugs (blood-thinners — saw palmetto may affect the blood’s ability to clot, and could interfere with blood-thinning drugs, including: Warfarin and Coumadin, Clopidogrel (Plavix), and Aspirin.
Oral contraceptives and hormone replacement therapy — Saw palmetto may reduce the number of estrogen and androgen receptors, and thus have hormone- like effects. It may make oral contraceptives less effective, raising the risk of unplanned pregnancy.
Dosage: 320 mg daily for one month to one year.
By using the same symptom scoring system (AUASI) as many studies in previous reviews, researchers were able to compare their findings with those of other high-quality studies with similar methodologies and outcome measures. Despite using an even higher dose of the extract, the results of this trial are remarkably consistent with previous conclusions: Saw palmetto is not an effective treatment for symptoms associated with BPH. Moreover, this trial had a broad base of participants similar to the population in a primary care practice, including patients who would typically choose a natural remedy for lower urinary tract symptoms (LUTS).
This concludes Part 4b of this series on nutrition and supplements. Next up will be Part 4c which will present both fish oil supplements and Vitamin B12 that we may use for better health. The final article of this series on supplements will be Part 4d.
I have gone into some depth on these because most people do not know much about the supplements they use, how they work to do their jobs, side effects and risks, and proper dosages.
Featured Photo at the top provided by Kevin Cline
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NeuroDocDuck (Dr. Driesen) is a doctor who specializes in neurology, and sports medicine. He is an Oregon alumnus, completing his medical education and training in the UK. He has been both a practicing clinician and professor, a well-known and respected diagnostician, an author, and has appeared on national television.
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