Form Of Dietary Supplements Research Articles

13C. The Effectiveness of Dietary Supplements for Pain Management

Focus Areas: Integrative Approaches to Care, Alleviating PainPain is often the most common medical condition for which patients choose complementary and alternative medicine (CAM), with dietary supplements representing the most common self-directed CAM treatment choice. However, with numerous dietary supplement choices on the market it often can be difficult for patients and clinicians to identify those with proven effectiveness for pain. This presentation will initially examine pain scenarios for which dietary supplements are commonly used (headache, joint pain, low back pain, and abdominal pain).Subsequently, the presentation will examine the rationale for dietary supplements including the purported mechanism(s) of action and indirect benefit on pain sequelea such as depression and fatigue. Finally, the presentation will provide the rationale for use and overview of currently available dietary supplement formulations that have demonstrated clinical effectiveness in various pain states. At the conclusion of this session, clinicians should gain great understanding of the importance of clinically tested dietary supplement formulations as well as counseling strategies for guiding patients toward evidence-based choices to optimize pain care.

Defining “Phthalates”

Defining “Phthalates”

Determination of Glucosamine and Carisoprodol in Pharmaceutical Formulations by LC with Pre-Column Derivatization and UV Detection

A simple and reliable precolumn derivatization liquid chromatography method with ultraviolet detection has been developed and validated for the analysis of glucosamine (GS) in various dietary supplement formulations and raw materials. Additionally, the proposed method was used for analysis of carisoprodol (CR) found in ternary mixture with paracetamol (PR) and caffeine (CF). The linearity ranges were 1-100 μg/mL for GS, 1-150 μg/mL for CR, PR and CF. Derivatization was used with 1,2-naphthoquinone-4-sulphonic acid sodium salt in the presence of borate buffer. Chromatographic separation of GS-naphthoquinone derivative was achieved by using a mixture of acetonitrile and water (pH 7.3 adjusted with 0.1 M NaOH) in the ratio 10:90, v/v and flow-rate of 1.0 mL/min. UV detection was carried out at 280 nm. For PR, CF, and CR-naphthoquinone derivative, the chromatographic separation was achieved by using mixture of acetonitrile and 20 mM KH(2)PO(4) (pH 3.0 adjusted with phosphoric acid) in the ratio 20:80, v/v and flow-rate of 1.0 mL/min. UV detection was carried out at 275 nm. The limits of detection were 37.2, 35.9, 30.4 and 40.0 ng/mL for GS, CR, PR and CF, respectively.

Identification of Phthalates in Medications and Dietary Supplement Formulations in the United States and Canada

Background: In animal studies, some ortho-phthalates, including di(2-ethylhexyl) phthalate (DEHP) and di-n-butyl phthalate (DBP), have been shown to be reproductive and developmental toxicants. Human studies show widespread population exposure to background levels of phthalates. Limited evidence suggests that particularly high exposure levels may result from orally ingested medicinal products containing phthalates as excipients (inactive ingredients).Objective: In this study we aimed to identify and describe the scope of prescription (RX) and nonprescription (over-the-counter; OTC) medicinal products and dietary supplements marketed in the United States and Canada since 1995 that include phthalates as excipients.Methods: We used lists of modified-release drug products to identify potential drug products. Inclusion of phthalates was verified using available electronic databases, print references, published package inserts, product packages, and direct communication from manufacturers. Additional products were identified using Internet searches utilizing keywords for phthalates.Results: Based on labeling information, 6 RX drug products included DBP as an excipient, and 45 specified the use of diethyl phthalate (DEP). Phthalate polymers with no known toxicity—hypromellose phthalate (HMP), cellulose acetate phthalate (CAP), and polyvinyl acetate phthalate (PVAP)—were included in 75 RX products. Three OTC drug and dietary supplement products listed DBP, 64 listed DEP, and > 90 indicated inclusion of polymers.Conclusions: Numerous RX and OTC drug products and supplements from a wide range of therapeutic categories may use DBP or DEP as excipients in oral dosage forms. The potential effects of human exposure to these phthalates through medications are unknown and warrant further investigation.

Chitosan analysis using acid hydrolysis and HPLC/UV

In this study, a method for the characterization and quantification of chitosan was designed using acid hydrolysis, glucosamine derivatization, and high performance liquid chromatography. Based on a kinetic study of acid hydrolysis, we have demonstrated that chitosan can be quantitatively hydrolyzed into glucosamine in 6 h with either 10 M hydrochloric acid (HCl) at 105 °C, or 12 M HCl at 90 °C. Following N-(9-fluorenylmethoxycarbonyloxy) succinimide (Fmoc-OSu) derivatization, the glucosamine content can be separated from the rest of the hydrolysates and quantified using reverse-phase HPLC with UV detection. This method was validated for linearity, precision (repeatability and reproducibility), and accuracy using both chitosan and a dietary supplement formulation containing chitosan.

Effect of a commercially-available algal phlorotannins extract on digestive enzymes and carbohydrate absorption in vivo

The ability of naturally occurring polyphenols and phlorotannins (PHTs) from some species of brown seaweeds to inhibit α-amylase and α-glucosidase enzymes in vitro has already been demonstrated. This study aimed at validating the efficacy of a new food ingredient extracted from Ascophyllum nodosum and Fucus vesiculosus PHTs at inhibiting digestive enzymes in vitro and slowing carbohydrate absorption in vivo. In vitro, the PHT extract completely inhibited in a dose-dependent fashion α-amylase and α-glucosidase with very low IC 50 values compared to other plant polyphenols. In animals, the PHT extract was able to reduce the normal increase in postprandial blood glucose seen 30 min after a meal by 90% (p < 0.05), and consecutively reduce peak insulin secretion by 40%. These results demonstrate the potency of this specific PHT extract to beneficially modulate carbohydrate digestion and assimilation, in a way that would be suitable for use in foods and dietary supplement formulations.

A review of the receptor-binding properties of p-synephrine as related to its pharmacological effects.

Bitter orange (Citrus aurantium) extract and its primary protoalkaloid p-synephrine are used widely in weight loss/weight management and sports performance products. Because of structural similarities, the pharmacological effects of p-synephrine are widely assumed to be similar to those of ephedrine, m-synephrine (phenylephrine), and endogenous amine neurotransmitters as norepinephrine and epinephrine. However, small structural changes result in the receptor binding characteristics of these amines that are markedly different, providing a plausible explanation for the paucity of adverse effects associated with the wide-spread consumption of p-synephrine in the form of dietary supplements as well as in various Citrus foods and juices. This paper summarizes the adrenoreceptor binding characteristics of p-synephrine relative to m-synephrine, norepinephrine, and other amines as related to the observed pharmacological effects.

Rapid screening test for adulteration in raw materials of dietary supplements

Fourier transform infrared (FTIR) spectroscopy with attenuated total reflectance (ATR) sampling was evaluated for use in screening for adulteration in raw materials used in the formulation and manufacture of dietary supplements. ATR requires minimal-to-no sample preparation and the method runs in less than ten minutes, providing a robust, rapid screening test for a variety of possible adulterants in the raw materials of dietary supplements. Spectral comparison methods targeting structural similarities of known adulterants were developed. In this study, FTIR-ATR was used to detect the presence of known adulterants intentionally spiked into dietary ingredients, including erectile dysfunction drugs, steroids, weight loss drugs and Melamine.

Use of dietary supplements by breast cancer patients undergoing conventional cancer treatment

Background:Many breast cancer patients use some form of dietary supplement (DS) to complement their conventional cancer treatment, in the hope that they might lessen the side effects of treatment, improve quality of life, give a greater sense of control, and reduce stress. This pilot study assessed the level of DS usage by breast cancer patients undergoing conventional cancer treatment, and their concerns about the use of DS.Method:A cross-sectional descriptive survey in three breast cancer centers in Hong Kong using face-to-face interviewing was performed.Results:Of 82 female Chinese breast cancer patients who completed the survey, 99% reported that they had been using DS since their cancer was diagnosed. The most frequently used DS were Chinese herbal medicines, and patients spent about US$258 on DS every month. The reason given for using DS was to enhance their recovery from cancer, but at the same time the patients had safety concerns. However, most patients did not feel able to discuss these concerns with health professionals.Conclusion:The majority of the patients had some safety concerns, and said that they would welcome detailed and reliable information on DS. The lack of reliable information on the potential risks and benefits of using such supplements as an adjuvant to conventional treatment and the reluctance of patients to discuss their use of DS with health professionals is a major area of concern that warrants further attention.

Novel medicinal mushroom blend suppresses growth and invasiveness of human breast cancer cells

Mushrooms are an integral part of Traditional Chinese Medicine (TCM), and have been used for millennia to prevent or treat a variety of diseases. Currently mushrooms or their extracts are used globally in the form of dietary supplements. In the present study we have evaluated the anticancer effects of the dietary supplement, MycoPhyto® Complex (MC), a novel medicinal mushroom blend which consists of a blend of mushroom mycelia from the species Agaricus blazei, Cordyceps sinensis, Coriolus versicolor, Ganoderma lucidum, Grifola frondosa and Polyporus umbellatus, and β-1,3-glucan isolated from the yeast, Saccharomyces cerevisiae. Here, we show that MC demonstrates cytostatic effects through the inhibition of cell proliferation and cell cycle arrest at the G2/M phase of highly invasive human breast cancer cells MDA-MB-231. DNA-microarray analysis revealed that MC inhibits expression of cell cycle regulatory genes (ANAPC2, ANAPC2, BIRC5, Cyclin B1, Cyclin H, CDC20, CDK2, CKS1B, Cullin 1, E2F1, KPNA2, PKMYT1 and TFDP1). Moreover, MC also suppresses the metastatic behavior of MDA-MB-231 by the inhibition of cell adhesion, cell migration and cell invasion. The potency of MC to inhibit invasiveness of breast cancer cells is linked to the suppression of secretion of the urokinase plasminogen activator (uPA) from MDA-MB-231 cells. In conclusion, the MC dietary supplement could have potential therapeutic value in the treatment of invasive human breast cancer.

Nutritional Supplement Use among Professional Baseball Players in Taiwan

The use of nutritional supplements in athletes is widespread. Studies showed that athletes consumed more supplements than the general population. Meanwhile, such use is particularly frequent among elite athletes. However, the data of supplementation practices among professional athletes was insufficient. PURPOSE: To survey the supplementation practices among the professional baseball players in Taiwan. METHODS: A survey of anonymous questionnaire was conducted to investigate the usage of nutritional supplements and source of information in 109 baseball players of Chinese Professional Baseball League (CPBL). Data was sought on the prevalence, type and reason of supplement used as well as source of information. RESULTS: Ninety seven percent of the players consumed sports drink and 83% players used some form of dietary supplements. Respondents took a total of 40 different supplements with each player using an average of 5.0± 3.2 different products. The most frequently used supplements were multiple vitamin/mineral (56%), vitamin B complex (48%), energy bar/jelly (33%), calcium (26%), vitamin C (24%), tablet of golden clam (22%), fish liver oil (20%), high protein (18%), and glucose (13%). The players took supplement for reducing/eliminating fatigue (79%), nutrients replacement (60%), gaining energy (47%), increasing physical ability (38%), and enhancing performance (35%). The major sources of the supplement information were from fellow athlete (61%), athletic trainer/strength and conditioning instructor (56%), dietitian (34%), friend (29%), and doctor (26%). CONCLUSION: This survey demonstrates that nutritional supplement use was common among the professional baseball players. Multiple vitamin/mineral was the most commonly used form of supplement. The major reason for use was reducing/ eliminating fatigue. In the future, nutritionist and dietitian should provide the nutritional education to not only the athletes but also the athletic trainers as well as strength and conditioning instructors since they are the closest link to athletes and often recommend the use of supplements.

The Role of Serotonin in Nonnormative Risky Choice: The Effects of Tryptophan Supplements on the “Reflection Effect” in Healthy Adult Volunteers

Risky decision-making involves weighing good and bad outcomes against their probabilities in order to determine the relative values of candidate actions. Although human decision-making sometimes conforms to rational models of how this weighting is achieved, irrational (or nonnormative) patterns of risky choice, including shifts between risk-averse and risk-seeking choices involving equivalent-value gambles (the "reflection effect"), are frequently observed. In the present experiment, we investigated the role of serotonin in decision-making under conditions of uncertainty. Fifteen healthy adult volunteers received a treatment of 3 g per day of the serotonin precursor, tryptophan, in the form of dietary supplements over a 14-day period, whereas 15 age- and IQ-matched control volunteers received a matched placebo substance. At test, all participants completed a risky decision-making task involving a series of choices between two simultaneously presented gambles, differing in the magnitude of their possible gains, the magnitude of their possible losses, and the probabilities with which these outcomes were delivered. Tryptophan supplements were associated with alterations in the weighting of gains and small losses perhaps reflecting reduced loss-aversion, and a marked and significant diminution of the reflection effect. We conclude that serotonin activity plays a significant role in nonnormative risky decision-making under conditions of uncertainty.

Single-Laboratory Validated Method for Determination of Nordihydroguaiaretic Acid in Chaparral-Containing Dietary Supplements

Nordihydroguaiaretic acid (NDGA) occurs naturally in chaparral (Larrea tridentate Coville), a plant which commonly grows in the Southwest United States and has been used for medicinal purposes by Native Americans indigenous to that region. In addition to its traditional use as a tea, manufacturers of dietary supplements have marketed chaparral-containing products in a variety of formulations. Because of the hepatotoxicity of NDGA, and its occurrence in regulated products, we have developed a method for the determination of NDGA in dietary supplements and have tested this method in several dietary supplement formulations. Products were extracted with 80% methanol, filtered, and analyzed by high-performance liquid chromatography. NDGA was detected and determined with both a diode array detector and negative-ion electrospray. Fragmentation in the triple-quadrupole mass spectrometer was obtained by collisional activation of the [M-H](-) ion. Collisional activation produced sufficient fragmentation to provide unambiguous identification. Lack of a stable isotope labeled internal standard has led us to compare quantitations based on UV detection with quantitations based on tandem mass spectrometry (MS/MS). Presence of NDGA was confirmed in several dietary supplement products. Quantitative results from the 2 detection methods were comparable for most products. The limit of quantitation using MS/MS was lower and fewer interferences were observed, although UV detection provided better linearity.

The Use of Dietary Supplements and Medications by Canadian Athletes at the Atlanta and Sydney Olympic Games

To learn more about the prevalence of dietary supplement and medication use by Canadian athletes in the Olympic Games in Atlanta 1996 and Sydney 2000. Data were collected from personal interviews with Canadian athletes who participated at the 1996 Atlanta and 2000 Sydney Olympic Games. The athletes were interviewed by Canadian physicians regarding the use of vitamins, minerals, nutritional supplements, and prescribed and over-the-counter medications. Of the 271 Canadian athletes who participated at the Atlanta Olympics, 257 athletes were interviewed; at the Sydney Olympics, 300 of 304 Canadian athletes were interviewed. A quantitative and qualitative description of the use of dietary supplements by Canadian athletes at the Atlanta and Sydney Olympics. At the Atlanta Games, 69% of the athletes used some form of dietary supplements, whereas 74% of the athletes used dietary supplements at the Sydney Games. Vitamins were taken by 59% of men and 66% of women in Atlanta, and 65% of men and 58% women in Sydney. Mineral supplements were used by 16% of men and 45% of women in Atlanta, and 30% of men and 21% of women in Sydney. Nutritional supplements were used by 35% of men and 43% of women in Atlanta, and 43% of men and 51% of women in Sydney. The most popular vitamins were multivitamins in both Olympics. The most popular mineral supplements were iron supplements. The most commonly used nutritional supplement in Atlanta was creatine (14%), but amino acids (15%) were the most commonly used nutritional supplement in Sydney. In Atlanta, 61% of the athletes were using some form of medication, 54% of the athletes were using medications in Sydney. Nonsteroidal antiinflammatory drugs (NSAIDS) were the most commonly used medications at both Olympic Games. Among all sports, the highest prevalence of vitamin use occurred in boxing (91%) in Atlanta and swimming (76%) in Sydney. Rowers (56%) and cyclists (73%) demonstrated the highest use of mineral supplements. Nutritional supplement use occurred most often in swimming (56%) and cycling (100%). The use of NSAIDs was highest in softball (60%) in Atlanta and gymnastics (100%) in Sydney. This review demonstrates that dietary supplement use was common among Canadian athletes at both the Atlanta and Sydney Olympic Games. There was a slight increase in total dietary supplement use at the Sydney Games. Widespread use of supplements, combined with an absence of evidence of their efficacy and a concern for the possibility of "inadvertent" doping, underscore the need for appropriately focused educational initiatives in this area.

National survey of dietary supplement policies in acute care facilities

Policies on the use of dietary supplements in acute care facilities were studied. A national online survey was conducted in 2004 to determine institutional policies and practices related to the use of dietary supplements. Directors of pharmacy in acute care settings were asked about the role of the pharmacy and therapeutics committee, the use of a nonformulary request process, the use of informed consent, requirements for written orders, mechanisms to identify dietary supplements, recording of supplement use in the pharmacy database, recording of supplement use in the medication administration record, prohibitions on dietary supplement use, storage of dietary supplements, reporting of adverse events, and the use of published references. Usable responses were received from 302 (25.4%) of 1189 pharmacy directors. Policies on dietary supplements were developed and implemented in 62% of facilities, with 38% of respondents indicating that no such policy existed. Policies most commonly required a written order by an authorized prescriber, documentation of use in the medication administration record, and a mechanism for identification of dietary supplements by a health care practitioner prior to use. Thirty percent of respondents with policies reported that they prohibited dietary supplement use, and 9% of those without policies prohibited use in practice. Most institutions allowed the use of a patient's own supply of supplements if ordered by an authorized prescriber. Supplements were most commonly stored at the nurses' station or in a patient drawer. The most commonly used reference was the Internet. Pharmacists had concerns about the consistency of dietary supplement formulations, the lack of FDA review of supplements, and the difficulty of identifying supplements and distinguishing reputable manufacturers. A survey of pharmacy directors in acute care facilities revealed that many had no formal policy regarding dietary supplements and had not implemented planning for such a policy.

Commercial Dietary Ingredients fromVitis viniferaL. Leaves and Grape Skins: Antioxidant and Chemical Characterization

This paper reports an attempt to functionally and chemically characterize commercial ingredients from Vitis vinifera L. grape skins, grape pomace, and leaves, which are used in the formulation of dietary antioxidant supplements. The antioxidant capacity of these ingredients was assessed for the first time by the oxygen radical absorbance capacity (ORAC) methodology. Ingredients from grape skins and pomace (n = 17) showed ORAC values from 1.38 to 21.4 mumol Trolox equivalents/mg whereas ingredients from leaves (n = 4) showed ORAC values from 1.52 to 2.55 mumol Trolox equivalents/mg. The high-performance liquid chromatography-diode array detection/electrospray ionization-mass sprectrometry analysis of anthocyanins and flavonols revealed the authenticity of the ingredients as derived from V. vinifera L. and confirmed large differences in their phenolic content and distribution. A progressive decline in both antioxidant capacity and total anthocyanin content of a grape skin ingredient (43 and 40% decrease, respectively) was observed over a 60 day storage period (45 degrees C and 75% relative humidity), demonstrating its poor stability under these conditions.

Quality Assessment of Commercial Dietary Antioxidant Products From Vitis vinifera L. Grape Seeds

: Phenolic preparations from Vitis vinifera L. grape seeds are products commonly used in the formulation of dietary antioxidant supplements. In this article, we used a methodology (the oxygen radical absorbance capacity, ORAC) to evaluate the in vitro antioxidant capacity of commercial dietary grape seed products and studied the relationship of the antioxidant capacity with the phenolic composition of these products. The ORAC value of the different brands of commercial products studied (n = 16) varied from 2.71 to 26.4 μmol Trolox equivalents/mg (≈10-fold difference). For four of these products, the batch-to-batch ORAC variation, expressed as a coefficient of variation of the mean, was 10.5% (n = 6), 13.1% (n = 3), 19.4% (n = 4), and 7.8% (n = 4). Analysis of monomeric and oligomeric flavan-3-ols by liquid chromatography-diode array detection (LC-DAD)/electrospray-mass spectrometry and procyanidins by thiolysis-LC-DAD also revealed large differences among the commercial grape seed products. Moreover, the ORAC value could be fitted to a regression model using variables from contents of individual phenolic compounds and procyanidins. The product-to-product and batch-to-batch variation in ORAC values and flavan-3-ol composition found among the commercial products studied demonstrated that they are poorly standardized, resulting in inconsistent composition and biological activity.

Contamination of dietary supplements and positive drug tests in sport

The use of dietary supplements is widespread in sport and most athletes competing at the highest level of competition use some form of dietary supplementation. Many of these supplements confer no performance or health benefit, and some may actually be detrimental to both performance and health when taken in high doses for prolonged periods. Some supplements contain excessive doses of potentially toxic ingredients, while others do not contain significant amounts of the ingredients listed on the label. There is also now evidence that some of the apparently legitimate dietary supplements on sale contain ingredients that are not declared on the label but that are prohibited by the doping regulations of the International Olympic Committee and of the World Anti-Doping Agency. Contaminants that have been identified include a variety of anabolic androgenic steroids (including testosterone and nandrolone as well as the pro-hormones of these compounds), ephedrine and caffeine. This contamination may in most cases be the result of poor manufacturing practice, but there is some evidence of deliberate adulteration of products. The principle of strict liability that applies in sport means that innocent ingestion of prohibited substances is not an acceptable excuse, and athletes testing positive are liable to penalties. Although it is undoubtedly the case that some athletes are guilty of deliberate cheating, some positive tests are likely to be the result of inadvertent ingestion of prohibited substances present in otherwise innocuous dietary supplements.

The use of dietary supplements in a community hospital comprehensive cancer center: implications for conventional cancer care

There is little data on the prevalence of use of dietary supplements in cancer, especially in light of the growing evidence that some dietary supplements can have adverse interactions with conventional cancer treatment. The purpose of this study was to investigate the use of dietary supplements among adult cancer patients in a community hospital comprehensive cancer center. A survey of 227 new adult cancer patients presenting for treatment for the first time at Cancer Treatment Centers of America at Midwestern Regional Medical Center, between November 2001 and October 2003. Patients completed the McCune Questionnaire, a validated instrument that captures information on the use of 56 dietary supplements in cancer, at admission to the hospital. Of the 227 patients, 73% used some form of dietary supplements during the 30 day period before the survey was conducted. Dietary supplement use was significantly higher (p = 0.04) in patients with colorectal (80%) and breast (75%) cancer as compared to patients with lung cancer (53%). Patients with stage II (86%) and III (76%) disease at diagnosis were more likely (p = 0.02) to use dietary supplements as compared to those with stage I (71%) disease at diagnosis, while those with stage IV (61%) disease at diagnosis were least likely to use them. Of the 80 patients who had received chemotherapy within the last 30 days, 71% had also used dietary supplements in that timeframe and 25% had consumed one or more herbal therapies that are suspected to have adverse interactions with chemotherapy. Of the 57 patients combining chemotherapy with dietary supplements, 52.6% did not consult a healthcare professional. In our study, twenty-five percent of patients receiving chemotherapy were concurrently using dietary supplements suspected to have adverse interactions with chemotherapy, usually relying on information sources other than healthcare professionals. Given the prevalence rates of these agents, healthcare providers should systematically inquire about them, and consider the potential for drug-dietary supplement interactions in treatment planning.

Ganoderma lucidum suppresses angiogenesis through the inhibition of secretion of VEGF and TGF-β1 from prostate cancer cells

Ganoderma lucidum ( G. lucidum) is a popular medicinal mushroom that has been used as a home remedy for the general promotion of health and longevity in East Asia. The dried powder of G. lucidum, which was recommended as a cancer chemotherapy agent in traditional Chinese medicine, is currently popularly used worldwide in the form of dietary supplements. We have previously demonstrated that G. lucidum induces apoptosis, inhibits cell proliferation, and suppresses cell migration of highly invasive human prostate cancer cells PC-3. However, the molecular mechanism(s) responsible for the inhibitory effects of G. lucidum on the prostate cancer cells has not been fully elucidated. In the present study, we examined the effect of G. lucidum on angiogenesis related to prostate cancer. We found that G. lucidum inhibits the early event in angiogenesis, capillary morphogenesis of the human aortic endothelial cells. These effects are caused by the inhibition of constitutively active AP-1 in prostate cancer cells, resulting in the down-regulation of secretion of VEGF and TGF-β1 from PC-3 cells. Thus, G. lucidum modulates the phosphorylation of Erk1/2 and Akt kinases in PC-3 cells, which in turn inhibits the activity of AP-1. In summary, our results suggest that G. lucidum inhibits prostate cancer-dependent angiogenesis by modulating MAPK and Akt signaling and could have potential therapeutic use for the treatment of prostate cancer.