Background: Anecdotal information and case reports suggest that intravenously administered vitamin C is used by Complementary and Alternate Medicine (CAM) practitioners. The scale of such use in the U.S. and associated side effects are unknown.
Methods and Findings: We surveyed attendees at annual CAM Conferences in 2006 and 2008, and determined sales of intravenous vitamin C by major U.S. manufacturers/distributors. We also queried practitioners for side effects, compiled published cases, and analyzed FDA’s Adverse Events Database. Of 199 survey respondents (out of 550), 172 practitioners administered IV vitamin C to 11,233 patients in 2006 and 8876 patients in 2008. Average dose was 28 grams every 4 days, with 22 total treatments per patient. Estimated yearly doses used (as 25g/50ml vials) were 318,539 in 2006 and 354,647 in 2008. Manufacturers’ yearly sales were 750,000 and 855,000 vials, respectively. Common reasons for treatment included infection, cancer, and fatigue. Of 9,328 patients for whom data is available, 101 had side effects, mostly minor, including lethargy/fatigue in 59 patients, change in mental status in 21 patients and vein irritation/phlebitis in 6 patients. Publications documented serious adverse events, including 2 deaths in patients known to be at risk for IV vitamin C. Due to confounding causes, the FDA Adverse Events Database was uninformative. Total numbers of patients treated in the US with high dose vitamin C cannot be accurately estimated from this study.
Conclusions: High dose IV vitamin C is in unexpectedly wide use by CAM practitioners. Other than the known complications of IV vitamin C in those with renal impairment or glucose 6 phosphate dehydrogenase deficiency, high dose intravenous vitamin C appears to be remarkably safe. Physicians should inquire about IV vitamin C use in patients with cancer, chronic, untreatable, or intractable conditions and be observant of unexpected harm, drug interactions,orbenefit.Introduction
Among the most enduring of alternative medical treatments, vitamin C (ascorbic acid, ascorbate) is also one of the most popular. In 2007, it was the most widely sold single vitamin, with sales of 884 million dollars in the US1 . Independent of its use to treat the deficiency disease scurvy, vitamin C has been used by non- mainstream physicians orally and parenterally for more than 60 years as a therapeutic agent [2–7]. Oral vitamin C is widely used by the public to prevent or treat infections, especially the common cold . In one of its more controversial applications, gram doses of vitamin C were promoted by the two-time Nobel Laureate Linus Pauling as a cancer treatment agent [9,10]. Anecdotal evidence led us to posit that intravenous (IV) vitamin C is still used by Complementary and Alternative Medicine (CAM) practitioners to treat diverse conditions including infections, autoimmune diseases, cancer and illnesses of uncertain origin [11–13].
Despite its purported popularity, the extent of use of IV vitamin C is unknown. Its use in CAM has not been well publicized by practitioners and their patients, and is likely to be unrecognized by mainstream physicians. Benefits if any and especially side effects of such use may be unreported or under-reported. It is useful to know if high dose IV vitamin C therapy is widely used, and if so how and for what, so that conventional physicians can improve patient care by identifying any ill effects or drug interactions, and reporting benefit if any.
New knowledge has elucidated possible mechanisms of action of IV vitamin C and for the first time made therapeutic effects biologically plausible . It is now known that IV but not oral administration of vitamin C produces pharmacologic plasma concentrations of the vitamin [15,16]. Past studies used oral and/ or IV routes inconsistently, making such studies, in retrospect, flawed and difficult to interpret . Recent in vitro experiments indicated that vitamin C only in pharmacologic concentrations killed cancer cells but not normal cells, and that the mechanism was via hydrogen peroxide formation . In vivo animal data indicated that hydrogen peroxide was produced selectively in extracellular fluid around normal and tumor tissues by pharma- cologic vitamin C concentrations [19,20]. At these concentrations, vitamin C slowed tumor growth [20,21]. Pharmacologic vitamin C concentrations produced in animals by parenteral administration were reproduced in patients in a recent phase I clinical trial .
Because of the new interest in IV vitamin C, coupled to need to characterize use and uncover side effects, we surveyed CAM practitioners anonymously. We also searched for side effects of IV vitamin C administration in the published medical literature and in the Food and Drug Administration (FDA) adverse events database, and estimated sales volumes of IV vitamin C preparations.
Our study obtained quantitative information that substantiated previous anecdotal reports. Despite unexpected wide use, we found side effects of vitamin C were surprisingly few when patients were properly screened. The findings in this paper will alert conventional practitioners about unrecognized wide use of IV vitamin C, will remind them to query patients about such use, and may help to uncover either unexpected adverse events or benefit and spur further research in this area.
Rice- and chili-containing foods are common in Asia. Studies suggest that rice is completely absorbed in the small bowel, produces little intestinal gas and has a low allergenicity. Several clinical studies have demonstrated that rice-based meals are well tolerated and may improve gastrointestinal symptoms in functional gastrointestinal disorders (FGID). Chili is a spicy ingredient commonly use throughout Asia. The active component of chili is capsaicin. Capsaicin can mediate a painful, burning sensation in the human gut via the transient receptor potential vanilloid-1 (TRPV1). Recently, the TRPV1 expressing sensory fibers have been reported to increase in the gastrointestinal tract of patients with FGID and visceral hypersensitivity. Acute exposure to capsaicin or chili can aggravate abdominal pain and burning in dyspepsia and IBS patients. Whereas, chronic ingestion of natural capsaicin agonist or chili has been shown to decrease dyspeptic and gastroesophageal reflux disease (GERD) symptoms. The high prevalence of spicy food in Asia may modify gastrointestinal burning symptoms in patients with FGID. Studies in Asia demonstrated a low prevalence of heartburn symptoms in GERD patients in several Asian countries. In conclusion rice is well tolerated and should be advocated as the carbohydrate source of choice for patients with FGID. Although, acute chili ingestion can aggravate abdominal pain and burning symptoms in FGID, chronic ingestion of chili was found to improve functional dyspepsia and GERD symptoms in small randomized, controlled studies.
Keywords: Chili pepper, Rice, Functional gastrointestinal disorder, Capsaicin, TRPV1 receptor
Complaints of gastrointestinal symptoms after food ingestion are common in patients with functional gastrointestinal disorders (FGID) and are reported in 25-64% of irritable bowel syndrome (IBS) patients.IBS patients often complain of food-related gastrointestinal symptoms secondary to more than one specific food. A recent population-based study in the USA demonstrated that 16.5% and 28.3% of IBS patients had intolerance to 1-2 food items and > 2 items, respectively. These statistics suggest that hyper-sensitivity to the ingestion of foods is common in IBS. Research studies also demonstrate that certain foods, such as chili, fructose or fructan containing foods and fatty foods, can affect gastrointestinal motility and sensation and induce gastrointestinal symptoms more than other foods.This suggests that certain foods, and not just the process of eating foods, can aggravate symptoms in patients with FGID. Therefore, modification of either eating habits (reducing meal size and/or the time of meals) or the composition of meals (avoiding specific food items) may benefit patients with FGID, and studies on the effects of food on gastrointestinal functions and symptoms are important.
The effects of food ingestion on gastrointestinal symptoms in patients with FGID have been extensively studied, mainly in Western countries and with Western diets. Moreover, information regarding the effects of typical Asian foods on gastrointestinal symptoms of FGID is quite limited. This review will focus on the effects of specific but widely used Asian diets/ingredients, "rice and chili or spicy foods," on gastrointestinal functions and their roles on the symptoms of FGID.
Characteristics of the Asian Diet
The Asian diet is characterized by a high-carbohydrate, high-fiber, low-fat, and low-meat protein composition. Typical Asian food generally consists of rice and vegetables as the major source of carbohydrate and fiber. Vegetable oil is a common source of fat, whereas fish, eggs, poultry, and pork are the main sources of protein. This is in contrast to Western diets, which are rich in animal fat and beef protein but lower in carbohydrate and fiber contents. In addition, Asian foods often consist of several ingredients, such as chili, to make the foods tastier.
CoQ10 has been considered for prevention and treatment of cardiovascular disease related to atherosclerosis, hypertension, diabetes and other common risk factors. LDL (“bad cholesterol”) in the walls of arteries can be oxidatively damaged and that may be an initiating event leading to atherosclerosis. In these cases, the antioxidant function of CoQ10 might be beneficial. There are other properties of CoQ10 that are of interest, such as its ability to decrease the amount of a specific substance on the surface of cells that can collect on the blood vessel walls (1).
An analysis of available research in 2003 found conflicting results. Some improvement in cardiac function was observed in some studies, but not confirmed in others (4).
CoQ10 is considered as a possible treatment for cardiomyopathy, which is an abnormality or disease of the cardiac muscle. Improvements in cardiac output have been found in some small studies. It has also been shown to help congestive heart failure as the result of coronary heart disease in other small studies. Again, there is a need for more large-scale clinical trials (1, 3).
Levels of CoQ10 have been considered as an independent predictor for outcome in patients with chronic heart failure. Those with lower levels have a higher risk of death. In one recent study, the correlation was strong enough for investigators to call for more interventional studies using CoQ10 to treat heart failure (4).
This same pattern repeats for almost all types of cardiovascular disease and treatment. From the treatment of angina (lack of blood supply to the heart muscle), to high blood pressure and damage of the lining of the blood vessels, there is some evidence of benefit from CoQ10 and a need for more studies (1).
I make sure that my patients' coq10 levels are assessed and they are treated accordingly.
1. Higdon, J. Coenzyme Q10. Micronutrient Information Center. Linus Pauling Institute. 2/2003. Updated 2/2007. lpi.oregonstate.edu/infocenter/othernuts/coq10/#deficiency (Accessed 5/27/2010)
2. 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. www.ahrq.gov/clinic/epcsums/antioxsum.htm.
3. Dallner, G, Stocker, R. Coenzyme Q10. Encyclopedia of dietary supplements, ed Paul M. Coates. Marcel Dekker, New York. 2005.
4. Molyneux, SL, Florkowski, CM, George, PM, et al. Coenzyme Q10: An Independent Predictor of Mortality in Chronic Heart Failure. J. Am. Coll. Cardiol. 2008;52;1435-1441.
Dr. Paunesky is board certified in Internal Medicine and Anti-Aging Medicine. She is also certified in Bariatric Medicine (Weight Loss). She relocated to Atlanta, Georgia after serving as a clinical staff hospitalist at the prestigious Cleveland Clinic Foundation of Cleveland, Ohio. She received her Bachelor of Science degree from Case Western Reserve in 1991 and her Medical degree from the University of Cincinnati in 1995. Subsequently, she completed an Internal Medicine residency at Case Western Metropolitan Hospital of Cleveland. After her residency, Dr. Paunesky served as a staff internist, hospitalist and bariatric physician at the Cleveland Clinic. She has been serving at the Renaissance Medical Center for over 9 years.
Dr. Paunesky is the first doctor in Atlanta, Georgia to become board certified by the American Board of Anti-Aging Medicine.
Dr. Paunesky's holistic approach encompasses both traditional and anti-aging medicine with state of the art hormone replacement therapy. This combined approach coupled with nutritional counseling is the way to a better, more productive quality of life. Her unique medical background and compassionate approach provides unprecedented healthcare to both men and women.Executives, professionals and physicians from all over the United States of America entrust Dr. Paunesky with their own and their family's healthcare.
For more information on Dr. Paunesky and the Renaissance Medical Center please visit: www.dr.paunesky.com
Various medications are traditionally used to induce ovulation in women with PCOS. A growing body of evidence now exists indicating that low-frequency electroacupuncture is as effective as commonly used medications in inducing ovulation. Furthermore, this form of acupuncture can benefit many of the hormonal imbalances seen in polycystic ovarian syndrome. Thousands of women worldwide use acupuncture therapy for PCOS and so I’d like to discuss how it works, and why it is so beneficial to induce ovulation.
General principles of how electroacupuncture stimulates the ovaries through the nervous system
Electroacupuncture has been found to profoundly effect the reproductive organs, through mechanisms in the sympathetic nervous system, endocrine system, and neuroendocrine system. When needles are inserted into certain points and stimulated in a specific manner, this produces a neurological reflex transmitted to the organ correlated with that nerve pathway. For example, needles inserted into the leg muscles below the knee, lower back, or abdomen in specific regions cause a response which measurably affects the ovary. In addition, the nervous system will transmit a signal to the brain, and the brain then emits a response which affects the organ from a central mechanism. These effects have been investigated through measurements of hormones, neuropeptides, and circulatory changes on both animals and humans receiving this specific type of electroacupuncture.
Nervous system alterations in PCOS
Evidence indicates that women with pcos have abnormal circulating levels of a neurohormone called β-endorphin. β-endorphin is known to increase insulin production and reduce insulin excretion by the liver, which is very much implicated in PCOS. It has also been found that women with PCOS have unusually high amounts of sympathetic nerve fibres in their ovaries. These nerve fibres cause unusual stimulation of the ovary by the sympathetic nervous system (the part of the nervous system associated with “flight or fight” responses in the body, among other processes). Stimulation of these nerve fibres can cause the ovaries to produce androgens, which then impair normal ovulation. Women with PCOS have also been found to have high amounts of nerve growth factors in their ovaries, something which is associated with high levels of sympathetic nervous system activity. Disturbances in central and peripheral β-endorphin release, high androgens, insulin resistance, abdominal obesity, and cardiovascular disease are associated with increased sympathetic nervous system activity, and all of these are also associated with the pathology of PCOS. In a recent study by Elizabet Stener-Vitorin in Sweden, direct intraneural testing found a strong correlation between levels of sympathetic nervous system activity and testosterone levels in women with PCOS. Those who had the highest amounts of sympathetic nervous system activity were found to have the highest testosterone levels and the most severe PCOS conditions.
What evidence exists for acupuncture inducing ovulation?
Several studies exist on low frequency electroacupuncture and ovulation induction. In one trial, the effect of a series of 14 electroacupuncture treatments on 24 anovulatory women with pcos was investigated. In 38% of these women, regular ovulation was induced. Three months after the last treatment, LH/FSH ratios and testosterone levels were significantly decreased, a sign of improvement in PCOS pathology. In another study done on a group of women given human menopausal gonadotrophin (a commonly used drug in the treatment of infertility), acupuncture was compared to hCG injections in order to assess its effect on ovulation. Traditionally hCG is given to stimulate ovulation during medicated cycles at fertility clinics. It was found that a single acupuncture treatment induced ovulation as effectively as the as the hCG injection and reduced the incidence of ovarian hyperstimulation syndrome, a painful side effect of medicated cycles. Other studies have also indicated enhanced ovarian response when acupuncture is added to medicated cycles. Female rats with PCOS induced by chronic exposure to DHT (a form of testosterone) were given low frequency electroacupuncture and physical exercise. The treatment increased the amount of healthy follicles in the ovaries, and significantly normalized cycles.
Effects of electroacupuncture on nervous system changes in PCOS
It has also been found that electro-acupuncture can regulate parts of the central nervous system related to dysfunction in PCOS. Specifically, beneficial effects on neurohormones such as GnRH(Gonadotropin releasing hormone) and androgen receptor proteins, indicate that electro-acupuncture significantly benefits the hypothalamic-pituitary-ovarian axis and through this can help to restore normal cycling. Electroacupuncture was also found in 3 recent studies to increase ovarian blood flow through effects on sympathetic nervous system pathways. In addition, it has been found in two studies to reduce high peripheral circulating β-endorphins in women with PCOS, and thereby improve insulin resistance. As sympathetic nerve activity appears to contribute to the development and maintenance of PCOS, the beneficial effects of electroacupuncture, and also exercise, may be mediated by nervous system modulation to the ovaries.
Electro-acupuncture appears to work through multiple pathways to disrupt the “vicious cycle” of PCOS. Even though much more research needs to be done to determine all of the mechanisms involved, its safety and low incidence of side effects makes it an excellent therapy to stimulate ovulation naturally for the many women who suffer with this disease.
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Carmina, E., Ditkoff, E.C., Malizia, G., Vijod, A.G., Janni, A., Lobo, R.A., 1992. Increased circulating levels of immunoreactive beta-endorphin in polycystic ovary syndrome is not caused by increased pituitary secretion. Am. J. Obstet. Gynecol. 167,
Chen, B.Y., Yu, J., 1991. Relationship between blood radioimmunoreactive beta-endorphin and hand skin temperature during the electro-acupuncture induction of ovulation. Acupunct. Electrother.
Lobo, R.A., Granger, L. R., Paul, W.L., Goebelsmann, U., Mishell Jr., D.R., 1983. Psychological stress and increases in urinary norepinephrine metabolites, platelet serotonin, and adrenal androgens in women with polycystic ovary syndrome. Am. J. Obstet. Gynecol. 145, 496–503.
Feng, Y., Johansson, J., Shao, R., Manneras, L., Fernandez-Rodriguez, J., Billig, H., Stener-Victorin, E., 2009. Hypothalamic neuroendocrine functions in rats with dihydrotestosterone-induced polycystic ovary syndrome: effects of low-frequency electroacupuncture. PLoS ONE 4, e6638. produces skeletal muscle vasodilation following antidromic stimulation of unmyelinated afferents in the dorsal root in rats. Neurosci. Lett. 283, 137–140.
Jin, C.L., Tohya, K., Kuribayashi, K., Kimura, M., Hirao, Y.H., 2009. Increased oocyte production after acupuncture treatment during superovulation process in mice. J. of Reprod. & Conception 20, 35–44.
Manneras, L., Cajander, S., Lonn, M., Stener-Victorin, E., 2009. Acupuncture and exercise restore adipose tissue expression of sympathetic markers and improve ovarian morphology in rats with dihydrotestosterone-induced PCOS. Am. J. Physiol. Regul. Integr. Comp. Physiol. 296, R1124–R1131.
Stener-Victorin, E., Wu, X., Effects and mechanisms of acupuncture in the reproductive system, Auton. Neurosci.(2010)
Stener-Victorin, E., Lindholm, C., 2004. Immunity and beta-endorphin concentrations in hypothalamus and plasma in rats with steroid-induced polycystic ovaries: effect of low-frequency electroacupuncture. Biol. Reprod. 70, 329–333.
Stener-Victorin, E., Waldenstrom, U., Tagnfors, U., Lundeberg, T., Lindstedt, G., Janson, P.O., 2006. Effects of electro-acupuncture on anovulation in women with polycystic ovary syndrome. Acta Obstet. Gynecol. Scand.
Stener-Victorin, E., Lundeberg, T., Waldenstrom, U., Manni, L., Aloe, L., Gunnarsson, S., Janson, P.O., 2000a. Effects of electro-acupuncture on nerve growth factor and ovarian morphology in rats with experimentally induced polycystic ovaries. Biol. Reprod. 63, 1497–1503.
Stener-Victorin, E., Lundeberg, T., Waldenstrom, U., Bileviciute-Ljungar, I., Janson, P.O., 2001. Effects of electro-acupuncture on corticotropin-releasing factor in rats with experimentally-induced polycystic ovaries. Neuropeptides 35, 227–231.
Stener-Victorin, E., Kobayashi, R., Kurosawa, M., 2003a. Ovarian blood ﬂow responses to electro-acupuncture stimulation at different frequencies and intensities in anaesthetized rats. Auton. Neurosci.: Basic and Clin. 108, 50–56.
Stener-Victorin, E., Lundeberg, T., Cajander, S., Aloe, L., Manni, L., Waldenstrom, U., Janson, P.O., 2003b. Steroid-induced polycystic ovaries in rats: effect of electro- acupuncture on concentrations of endothelin-1 and nerve growth factor (NGF), and expression of NGF mRNA in the ovaries, the adrenal glands, and the central nervous system. Reprod. Biol. Endocrinol. 1, 33.
Stener-Victorin, E., Fujisawa, S., Kurosawa, M., 2006. Ovarian blood ﬂow responses to electroacupuncture stimulation depend on estrous cycle and on site and frequency of stimulation in anesthetized rats. J. Appl. Physiol. 101, 84–91.
Stener-Victorin, E., Jedel, E., Manneras, L., 2008. Acupuncture in polycystic ovary syndrome: current experimental and clinical evidence. J. Neuroendocrinol. 20, 290–298.
Stener-Victorin, E., Jedel, E., Janson, P.O., Sverrisdottir, Y.B., 2009. Low-frequency electro-acupuncture and physical exercise decrease high muscle sympathetic nerve activity in polycystic ovary syndrome. Am.J.Physiol.Regul.Integr.Comp.Physiol. 297 (2), R387R395.
Zhao, H., Tian, Z.Z., Chen, B.Y., 2003a. An important role of corticotropin-releasing hormone in electroacupuncture normalizing the subnormal function of hypothalamus–pituitary–ovary axis in ovariectomized rats. Neurosci. Lett. 349, 25–28.
There is a rhythm in life. You see it everywhere in nature. Moon cycles, seasonal changes, circadian rhythms, migratory patterns, growth spurts, planting/harvesting times, etc. There is nothing static in nature. Everything is in a constant flux. The only thing that’s static is death. At least, that’s what we know for now. If there are rhythmic patterns in our bodies, doesn’t it make sense to give hormones (if a person’s symptomatic, deficient or has sub-optimal numbers) in a rhythmic pattern as well? This idea was actually brought forth by a person named TS Wiley. She’s trained as an anthropologist and unfortunately (or fortunately?) is not an MD. Otherwise, a lot of doctors, especially in the anti-aging community would have jumped onto the bandwagon of prescribing bioidentical hormones in a rhythmic manner. That is, changing the dose every so often, to mimic nature. Doctors, just like every one else, are creatures of habit. Nobody wants to mess with the status quo. A German philosopher named Arthur Schopenhauer put it succinctly, “All truth passes through three stages. First, it is ridiculed. Second, it is violently opposed. Third, it is accepted as being self-evident.” Anyway, hormonal imbalance is just one of the causes of accelerated, symptomatic aging. Other factors such as nutritional deficiencies, chronic inflammatory processes, toxicities, oxidative stress and mitochondrial dysfunction need to be addressed as well if a person wants to age well.