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Post #1 Red Flags and Beliefs Explained Assignment #1

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Post #1 Red Flags and Beliefs Explained Assignment #1

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Made by: Emily and Taya
Made together as a group

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Post #2 Red Flag: Appeal to Authority (Instagram Post & Article)

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Post #2 Red Flag: Appeal to Authority (Instagram Post & Article)

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Definition: Appeal of authority is the use of  authoritative imagery or people to endorse their product. Authoritative imagery creates the appearance of credibility to the product. This means the use of a well known celebrity, or doctors in white coats. This usually gives the product instant credibility and tricks people into products that are actually worthless.

Connection: Kim Kardashian is a celebrity influencer who is often seen representing new diet fads. This particular Flat Tummy Co. product is an appetite suppressant lollipop. A lot of her followers were interested but others believed she was promoting eating disorder culture and diet culture. These lollipops have not been reviewed to medical professionals. This example shows that just because a celebrity is showing the product people assume it is safe to use. https://www.dailymail.co.uk/femail/article-5736987/Appetite-suppressant-lollipops-promoted-Kim-Kardashian-supported-ONE-study.html

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Definition: All-natural marketing is based on supplement products that claim to cure diseases. These products are said to have 'organic,' or 'natural' ingredients. Although the product labels say 'all-natural,' this doesn't necessarily mean they are safe, or healthy.

Connection: This article relates to the concept of all-natural products because it describes the safety of these products. Multivitamin and calcium supplements are considered 'safe' as long as they are used properly. Supplements used for 'weight loss, boosting energy, etc.,' on the other hand, are not necessarily safe for our health. They may cause 'serious adverse events including stroke, organ failure, and death.' According to the article, "all-natural herbal supplements are adulterated by prescription, and over-the counter medications." It has been said that these "dietary supplements have caused about 50,000 adverse events annually" (https://onlinelibrary.wiley.com/doi/full/10.1002/dta.1855). This shows that we can't always trust the labels that we see on bottles.

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Abstract

The Dietary Supplement Health and Education Act of 1994 (DSHEA), which arbitrarily classified herbals and other medicinal products as dietary supplements, obscured fundamental differences between two classes of products. Authentic supplements to the diet, such as multivitamins or calcium, have nutritional value and are safe. Herbals are used worldwide as medicines, they do not supplement the diet, they may cause severe adverse events, and they should be regulated as medicines. DSHEA also prevented the Food and Drug Administration (FDA) from effectively regulating herbal supplements as medicines. One consequence of weak FDA regulatory oversight is the poor quality of herbals. FDA inspections of manufacturing facilities have revealed violations of good manufacturing practices in over half of facilities inspected, including unsanitary conditions and lack of product specifications. Moreover, many "all natural" herbals marketed for weight loss, enhancement of sexual health and improving sports performance are adulterated with prescription and over‐the‐counter medications that have caused adverse cardiovascular events. New procedures to authenticate the identity of plants used in herbals will neither detect adulteration by medications nor provide assurance of appropriate pharmacological activity or safety. Nonvitamin, nonmineral "supplements" should be regulated as medicines, but revision or repeal of DSHEA faces strong opposition in Congress. The marketing of botanical supplements is based on unfounded claims that they are safe and effective. Health professionals need to inform patients and the public that there is no reason to take herbal medicines whose composition and benefits are unknown, and whose risks are evident.

Nomenclature

Articles on dietary supplements frequently begin with: 'Over 60% of Americans take dietary supplements.' But what are they actually putting into their bodies, a multivitamin or a misnamed medicine? Prior to the Dietary Supplement Health and Education Act of 1994 (DSHEA), 1 the category of dietary supplements included only multivitamins and minerals. By arbitrarily classifying herbals and other medicinal products as dietary supplements, DSHEA obscured fundamental differences between two classes of products. There is no scientific basis for calling herbals 'supplements'. Authentic supplements, such as multivitamins or calcium, have nutritional value and are safe when used in recommended doses. Botanicals are used worldwide as medicines. They do not supplement the diet, and they may cause severe adverse effects. As noted by the late Dr Varro Tyler, an authority on the medicinal use of plant products, herbals are 'crude drugs of vegetable origin utilized for treatment of disease states'. 2

Because consumers believe that all dietary supplements are harmless, the new nomenclature greatly increased sales of herbals and other supplements, especially for weight loss, boosting energy, and promoting sexual vigor. Moreover, the legislation, which was essentially written by the supplement industry, prevents effective regulation of herbals and other medicinal supplements by the US Food and Drug Administration (FDA).

Quality control

In 2008, the FDA started inspections of facilities that manufacture dietary supplements. From 2008 to 2012, the agency found violations of good manufacturing procedures in half of the 450 firms inspected, and in two‐thirds of 204 inspections performed in the first half of 2012. 3 The violations included lack of recipes for the products and unsanitary conditions, such as infestation by rodents. In 2014, the FDA inspected 255 dietary supplement manufacturing facilities in the United States and 228 in other countries. 4 Common infractions included not conducting a test to verify the identity of a dietary ingredient and/or 'not establishing product specifications for the identity, purity, strength, and/or composition of the finished dietary supplement'. An average of six infractions were noted at facilities that received a notice of noncompliance.

In a study of commercial herbal products, DNA was recovered from 91% of 44 samples made by 12 companies. 5 DNA barcoding analyses revealed that only 2/12 companies provided products that contained DNA of the plants listed on the label, and product substitution was noted in 30/44 samples. Fifty‐nine percent of herbals contained plant species not listed on the labels, and 33% contained DNA that matched rice, soybeans, and wheat, potential allergens which were not listed on the label. Some of the unlisted herbals, including senna and feverfew, are potentially toxic.

The New York State Attorney General commissioned DNA barcoding testing of 78 bottles of commercial herbal supplements sold by Walgreens, Walmart, Target, and GNC. 6 No DNA from the herb listed on the label was found in 4/5 bottles. In addition, the bottles often contained fillers, including rice, asparagus, and houseplants. A bottle of ginkgo biloba that was claimed to be wheat‐free and gluten‐free contained wheat, houseplants, and powdered radish. Concerns have been raised that the absence of DNA may be an artifact caused by its destruction during the manufacturing process. In response to these findings, GNC announced the institution of new procedures to authenticate the plants used in its supplements, and to test for common allergens. 7

Adulteration

Many 'all‐natural' herbal supplements are adulterated by prescription and over‐the‐counter medications. 8, 10 To escape detection by regulatory agencies, many PDE‐5 analogues have been synthesized. Seventy‐five percent of sexual enhancement supplements seized in the Netherlands contained PDE‐5 analogues. 11 There are eleven different families of phosphodiesterases that are active in a variety of metabolic processes. The FDA‐approved PDE‐5 medications inhibit only one family, but less specific analogues may inhibit receptors found in many organs, and their safety has not been studied. 10 9 Weight loss products frequently contain sibutramine, which the FDA withdrew from the market because of its association with strokes and cardiovascular events. Many supplements for the enhancement of athletic performance contain analogues of amphetamines, and supplements for sexual health frequently contain sildenafil or other phosphodiesterase‐5 (PDE‐5) inhibitors.

In a letter addressed to supplement manufacturers, FDA Commissioner Hamburg noted that the agency had 'issued warnings about 300 tainted products that can cause serious adverse events, including stroke, organ failure and death'. 12 Some adulterated products remain in the marketplace even after recalls. 13 Twenty‐seven supplements recalled because of adulteration were tested at least six months after being recalled. Sixty‐three percent (17/27) contained the same pharmaceutical adulterant identified previously by the FDA, and six contained one or more additional banned ingredients. Adulterated herbal supplements remain in the marketplace because the FDA's authority to mandate removal of supplements from the market is limited by DSHEA, and the fines for violations are small compared to the profits.

Because of concerns about purity and safety, some authors and health leaders recommend buying only supplements that have been approved by the US Pharmacopeial Convention (USP). The USP is an independent, non‐profit organization that provides analyses of food ingredients, medicines, and dietary supplements to improve the quality and safety of those products. The USP claims that analyses in its new Herbal Compendium 'establish standards for the identity, strength, quality and purity" of herbal products'. 14 USP tests provide useful information about contamination by microbial products, metals, and pesticides, and confirm the identity of the plant. However, analyses for the presence of all undeclared pharmaceutical compounds are not performed because of the enormous number of pharmaceuticals and novel analogues. Moreover, the meaning of USP's claim about verifying 'strength' of the herbals is unclear. Strength implies pharmacological activity, but the monographs provide no data about activity, which would be difficult to do because the active ingredients of most herbals have not been identified. The use of marker compounds for standardization does not provide assurance of pharmacological activity. Unqualified claims that USP analyses provide assurance of purity, quality, and strength are not justified by the data provided. In summary, new procedures to improve the quality of herbals will not guarantee either purity or standardized pharmacological activity.

Safety

A major factor in the promotion of herbals is the claim that they are gentle and safe because they are natural, in contrast to foreign, powerful, and toxic purified medications. In reality, the active ingredients of herbals are chemicals that act on the body in the same manner as purified medications, and have similar potential for benefit or harm. For example, Aristolochia sp. plants have been used worldwide in botanicals for over 1000 years. They were recently found to cause outbreaks of aristolochic acid nephropathy: interstitial nephritis, renal failure, and carcinomas of the upper urinary tract. 15 Naturally occurring aristolochic acids are among the most potent human carcinogens known.

Until recently, manufacturers were not required to report adverse events caused by supplements to the FDA, so most of our knowledge of supplement toxicity has come from Poison Control Centres and Emergency Rooms. 16 The FDA has estimated that dietary supplements cause 50 000 adverse events annually. 17 The most common adverse events are hepatic and renal damage, similar to those caused by FDA‐approved medications. A prospective study of drug‐induced liver disease found that approximately 20% of cases of acute liver failure in the United States were associated with the consumption of dietary supplements. 18 The FDA issues class I recalls of drug products for which there is a reasonable probability that use or exposure will cause serious adverse consequences or death. Moreover, from January 2004 through December 2012, 51% of recalled products were dietary supplements that were adulterated by unapproved drugs. 19

Efficacy

Claims for the efficacy of plant extracts are based on their long history of use, and on older clinical trials funded by manufacturers. Systematic reviews and meta‐analyses of those trials concluded that they were uninterpretable because of defects in design and interpretation, and publication bias. 20 Rigorous clinical trials supported by the National Institute of Health have found no benefit beyond a placebo effect for a number of popular herbals and supplements, including Echinacea, ginkgo biloba, ginseng, black cohosh, isoflavones, saw palmetto, and glucosamine. 21 Although some medications currently in use were originally identified in plant extracts, the vast majority of herbals have not been evaluated in clinical trials. Their perceived efficacy is based on traditional teaching and on placebo effects.

Conclusions

A fundamental question has been overlooked in recent articles about the quality of plant extracts: Is there any reason to take herbals? Their marketing is based primarily on the unfounded claims that they are safe and effective. Their only potential advantages - lower costs and the convenience of avoiding medical appointments - are outweighed by their hazards and uncertain efficacy.

Herbals and other medicinal products that were designated as supplements by DSHEA should be regulated as medicines. That would require revision or repeal of DSHEA, which is arguably the worst health care legislative act of the twentieth century. 22 Although efforts to amend DSHEA have been blocked by influential congressmen who supported its passage, they should be continued. However, the immediate need is to provide better information to the public. Most supplements are self‐prescribed, and people use them based on misleading information on the Internet and in the media. Health professionals need to communicate more effectively to patients and to the public that there is no reason to consume products whose benefits are unknown and whose risks are evident.

Number of times cited according to CrossRef: 37

Donald M. Marcus, Alternative therapies in academic medical centers compromise evidence-based patient care, Journal of Clinical Investigation, 10.1172/JCI137561,

The Impact of Natural Product Dietary Supplements on Patients with Gout: A Systematic Review and Meta-Analysis of Randomized Controlled Trials, Evidence-Based Complementary and Alternative Medicine, 10.1155/2020/7976130, (1-10), 2020,

Ce Shi, Peng Wang, Shriya Airen, Craig Brown, Zhiping Liu, Justin H. Townsend, Jianhua Wang, Hong Jiang, Nutritional and medical food therapies for diabetic retinopathy, Eye and Vision, 10.1186/s40662-020-00199-y, 1, 7,

What are the beliefs and behaviours related to sport nutrition supplements, particularly regarding UAE regulatory issues, among male fitness centre members in Dubai?, Clinical Epidemiology and Global Health, 10.1016/j.cegh.2020.02.027,

Suspected‐target and non‐targeted screenings of phosphodiesterase 5 inhibitors in herbal remedies using liquid chromatography-quadrupole time‐of‐flight-mass spectrometry, Drug Testing and Analysis, 10.1002/dta.2861, 0, 0,

Magdalena Ratajczak, Dorota Kaminska, Agata Światły-Błaszkiewicz, Jan Matysiak, Quality of Dietary Supplements Containing Plant-Derived Ingredients Reconsidered by Microbiological Approach, International Journal of Environmental Research and Public Health, 10.3390/ijerph17186837, 18, (6837), 17,

Prevalence and Use of Dietary Supplements Among Pharmacy Students in Saudi Arabia
, Risk Management and Healthcare Policy, 10.2147/RMHP.S256656, (1523-1531), Volume 13,

Fluorescence polarisation for high‐throughput screening of adulterated food products via phosphodiesterase 5 inhibition assay, Drug Testing and Analysis, 10.1002/dta.2926, 0, 0,

Testosterone Imposters: An Analysis of Popular Online Testosterone Boosting Supplements, The Journal of Sexual Medicine, 10.1016/j.jsxm.2018.12.008, 2, (203-212), 16,

Armando E. González-Stuart, José O. Rivera, Herbal Weight Loss Supplements, Dietary Interventions in Liver Disease, 10.1016/B978-0-12-814466-4.00014-8, (175-181),

Amitava Dasgupta, Effects of herbal supplements on clinical laboratory test results, Accurate Results in the Clinical Laboratory, 10.1016/B978-0-12-813776-5.00018-2, (295-318),

Susanna B. Mierau, Ann M. Neumeyer, Metabolic interventions in Autism Spectrum Disorder, Neurobiology of Disease, 10.1016/j.nbd.2019.104544, (104544),

Jozaa Z. AlTamimi, Awareness of the Consumption of Dietary Supplements among Students in a University in Saudi Arabia, Journal of Nutrition and Metabolism, 10.1155/2019/4641768, (1-10), 2019,

Bart I. Roman, Essay: Avoiding unfounded health claims on small molecules in scientific literature, Bioorganic Chemistry, 10.1016/j.bioorg.2019.02.002,

Amitava Dasgupta, Antiinflammatory Herbal Supplements, Translational Inflammation, 10.1016/B978-0-12-813832-8.00004-2, (69-91),

Chemical Barcoding: A Nuclear-Magnetic-Resonance-Based Approach To Ensure the Quality and Safety of Natural Ingredients, Journal of Agricultural and Food Chemistry, 10.1021/acs.jafc.9b01066,

Kelly A. Shipkowski, Joseph M. Betz, Linda S. Birnbaum, John R. Bucher, Paul M. Coates, D. Craig Hopp, Duffy MacKay, Hellen Oketch-Rabah, Nigel J. Walker, Cara Welch, Cynthia V. Rider, Naturally complex: Perspectives and challenges associated with Botanical Dietary Supplement Safety assessment, Food and Chemical Toxicology, 10.1016/j.fct.2018.04.007, (963-971), 118,

Akram Ghasemi Dastjerdi, Maryam Akhgari, Artin Kamali, Zahra Mousavi, Principal component analysis of synthetic adulterants in herbal supplements advertised as weight loss drugs, Complementary Therapies in Clinical Practice, 10.1016/j.ctcp.2018.03.007, (236-241), 31,

Analysis of Pharmacologic Adulteration in Dietary Supplements by Capillary Zone Electrophoresis Using Simultaneous Contactless Conductivity and UV Detection, Chromatographia, 10.1007/s10337-018-3496-2, 4, (689-698), 81,

Isolation and Analysis of Antioxidant Phytochemicals from Black Chokeberry, Maqui, and Goji Berry Dietary Supplements, Advances in Plant Phenolics: From Chemistry to Human Health, 10.1021/bk-2018-1286.ch001, (3-19),

Over-the-Counter "Adrenal Support" Supplements Contain Thyroid and Steroid-Based Adrenal Hormones, Mayo Clinic Proceedings, 10.1016/j.mayocp.2017.10.019, 3, (284-290), 93,

Herbal Dietary Supplements for Erectile Dysfunction: A Systematic Review and Meta-Analysis, Drugs, 10.1007/s40265-018-0897-3, 6, (643-673), 78,

Armando González-Stuart, José O. Rivera, Yellow Oleander Seed, or "Codo de Fraile" ( Thevetia spp.): A Review of Its Potential Toxicity as a Purported Weight-Loss Supplement , Journal of Dietary Supplements, 10.1080/19390211.2017.1353565, 3, (352-364), 15,

Sidney J. Stohs, Harry G. Preuss, What Health Care Professionals Should Know about the Regulation and Safety of Dietary Supplements, Journal of the American College of Nutrition, 10.1080/07315724.2016.1275065, 4, (306-309), 36,

Bill J Gurley, John S Markowitz, David Keith Williams, Gary W Barone, Practical considerations when designing and conducting clinical pharmacokinetic herb-drug interaction studies, International Journal of Pharmacokinetics, 10.4155/ipk-2016-0009, 1, (57-69), 2,

Piotr Rzymski, Monika Jaśkiewicz, Microalgal food supplements from the perspective of Polish consumers: patterns of use, adverse events, and beneficial effects, Journal of Applied Phycology, 10.1007/s10811-017-1079-5, 4, (1841-1850), 29,

Bryn Nelson, Regulatory roulette, Cancer Cytopathology, 10.1002/cncy.21861, 4, (227-228), 125,

Bryan E. Denham, When contaminated dietary supplements cause positive drug tests: methylhexaneamine as a doping agent in sport, International Journal of Sport Policy and Politics, 10.1080/19406940.2017.1348963, 4, (677-689), 9,

Neilson M. Mathews, Prohibited Contaminants in Dietary Supplements, Sports Health: A Multidisciplinary Approach, 10.1177/1941738117727736, (194173811772773),

Abstract

The Dietary Supplement Health and Education Act of 1994 (DSHEA), which arbitrarily classified herbals and other medicinal products as dietary supplements, obscured fundamental differences between two classes of products. Authentic supplements to the diet, such as multivitamins or calcium, have nutritional value and are safe. Herbals are used worldwide as medicines, they do not supplement the diet, they may cause severe adverse events, and they should be regulated as medicines. DSHEA also prevented the Food and Drug Administration (FDA) from effectively regulating herbal supplements as medicines. One consequence of weak FDA regulatory oversight is the poor quality of herbals. FDA inspections of manufacturing facilities have revealed violations of good manufacturing practices in over half of facilities inspected, including unsanitary conditions and lack of product specifications. Moreover, many "all natural" herbals marketed for weight loss, enhancement of sexual health and improving sports performance are adulterated with prescription and over‐the‐counter medications that have caused adverse cardiovascular events. New procedures to authenticate the identity of plants used in herbals will neither detect adulteration by medications nor provide assurance of appropriate pharmacological activity or safety. Nonvitamin, nonmineral "supplements" should be regulated as medicines, but revision or repeal of DSHEA faces strong opposition in Congress. The marketing of botanical supplements is based on unfounded claims that they are safe and effective. Health professionals need to inform patients and the public that there is no reason to take herbal medicines whose composition and benefits are unknown, and whose risks are evident.

Nomenclature

Articles on dietary supplements frequently begin with: 'Over 60% of Americans take dietary supplements.' But what are they actually putting into their bodies, a multivitamin or a misnamed medicine? Prior to the Dietary Supplement Health and Education Act of 1994 (DSHEA), the category of dietary supplements included only multivitamins and minerals. By arbitrarily classifying herbals and other medicinal products as dietary supplements, DSHEA obscured fundamental differences between two classes of products. There is no scientific basis for calling herbals 'supplements'. Authentic supplements, such as multivitamins or calcium, have nutritional value and are safe when used in recommended doses. Botanicals are used worldwide as medicines. They do not supplement the diet, and they may cause severe adverse effects. As noted by the late Dr Varro Tyler, an authority on the medicinal use of plant products, herbals are 'crude drugs of vegetable origin utilized for treatment of disease states'.

Because consumers believe that all dietary supplements are harmless, the new nomenclature greatly increased sales of herbals and other supplements, especially for weight loss, boosting energy, and promoting sexual vigor. Moreover, the legislation, which was essentially written by the supplement industry, prevents effective regulation of herbals and other medicinal supplements by the US Food and Drug Administration (FDA).

Quality control

In 2008, the FDA started inspections of facilities that manufacture dietary supplements. From 2008 to 2012, the agency found violations of good manufacturing procedures in half of the 450 firms inspected, and in two‐thirds of 204 inspections performed in the first half of 2012. The violations included lack of recipes for the products and unsanitary conditions, such as infestation by rodents. In 2014, the FDA inspected 255 dietary supplement manufacturing facilities in the United States and 228 in other countries. Common infractions included not conducting a test to verify the identity of a dietary ingredient and/or 'not establishing product specifications for the identity, purity, strength, and/or composition of the finished dietary supplement'. An average of six infractions were noted at facilities that received a notice of noncompliance.

In a study of commercial herbal products, DNA was recovered from 91% of 44 samples made by 12 companies. DNA barcoding analyses revealed that only 2/12 companies provided products that contained DNA of the plants listed on the label, and product substitution was noted in 30/44 samples. Fifty‐nine percent of herbals contained plant species not listed on the labels, and 33% contained DNA that matched rice, soybeans, and wheat, potential allergens which were not listed on the label. Some of the unlisted herbals, including senna and feverfew, are potentially toxic.

The New York State Attorney General commissioned DNA barcoding testing of 78 bottles of commercial herbal supplements sold by Walgreens, Walmart, Target, and GNC. No DNA from the herb listed on the label was found in 4/5 bottles. In addition, the bottles often contained fillers, including rice, asparagus, and houseplants. A bottle of ginkgo biloba that was claimed to be wheat‐free and gluten‐free contained wheat, houseplants, and powdered radish. Concerns have been raised that the absence of DNA may be an artifact caused by its destruction during the manufacturing process. In response to these findings, GNC announced the institution of new procedures to authenticate the plants used in its supplements, and to test for common allergens.

Adulteration

Many 'all‐natural' herbal supplements are adulterated by prescription and over‐the‐counter medications. Weight loss products frequently contain sibutramine, which the FDA withdrew from the market because of its association with strokes and cardiovascular events. Many supplements for the enhancement of athletic performance contain analogues of amphetamines, and supplements for sexual health frequently contain sildenafil or other phosphodiesterase‐5 (PDE‐5) inhibitors. To escape detection by regulatory agencies, many PDE‐5 analogues have been synthesized. Seventy‐five percent of sexual enhancement supplements seized in the Netherlands contained PDE‐5 analogues. There are eleven different families of phosphodiesterases that are active in a variety of metabolic processes. The FDA‐approved PDE‐5 medications inhibit only one family, but less specific analogues may inhibit receptors found in many organs, and their safety has not been studied.

In a letter addressed to supplement manufacturers, FDA Commissioner Hamburg noted that the agency had 'issued warnings about 300 tainted products that can cause serious adverse events, including stroke, organ failure and death'. Some adulterated products remain in the marketplace even after recalls. Twenty‐seven supplements recalled because of adulteration were tested at least six months after being recalled. Sixty‐three percent (17/27) contained the same pharmaceutical adulterant identified previously by the FDA, and six contained one or more additional banned ingredients. Adulterated herbal supplements remain in the marketplace because the FDA's authority to mandate removal of supplements from the market is limited by DSHEA, and the fines for violations are small compared to the profits.

Because of concerns about purity and safety, some authors and health leaders recommend buying only supplements that have been approved by the US Pharmacopeial Convention (USP). The USP is an independent, non‐profit organization that provides analyses of food ingredients, medicines, and dietary supplements to improve the quality and safety of those products. The USP claims that analyses in its new Herbal Compendium 'establish standards for the identity, strength, quality and purity" of herbal products'. USP tests provide useful information about contamination by microbial products, metals, and pesticides, and confirm the identity of the plant. However, analyses for the presence of all undeclared pharmaceutical compounds are not performed because of the enormous number of pharmaceuticals and novel analogues. Moreover, the meaning of USP's claim about verifying 'strength' of the herbals is unclear. Strength implies pharmacological activity, but the monographs provide no data about activity, which would be difficult to do because the active ingredients of most herbals have not been identified. The use of marker compounds for standardization does not provide assurance of pharmacological activity. Unqualified claims that USP analyses provide assurance of purity, quality, and strength are not justified by the data provided. In summary, new procedures to improve the quality of herbals will not guarantee either purity or standardized pharmacological activity.

Safety

A major factor in the promotion of herbals is the claim that they are gentle and safe because they are natural, in contrast to foreign, powerful, and toxic purified medications. In reality, the active ingredients of herbals are chemicals that act on the body in the same manner as purified medications, and have similar potential for benefit or harm. For example, Aristolochia sp. plants have been used worldwide in botanicals for over 1000 years. They were recently found to cause outbreaks of aristolochic acid nephropathy: interstitial nephritis, renal failure, and carcinomas of the upper urinary tract. Naturally occurring aristolochic acids are among the most potent human carcinogens known.

Until recently, manufacturers were not required to report adverse events caused by supplements to the FDA, so most of our knowledge of supplement toxicity has come from Poison Control Centres and Emergency Rooms. The FDA has estimated that dietary supplements cause 50 000 adverse events annually. The most common adverse events are hepatic and renal damage, similar to those caused by FDA‐approved medications. A prospective study of drug‐induced liver disease found that approximately 20% of cases of acute liver failure in the United States were associated with the consumption of dietary supplements. The FDA issues class I recalls of drug products for which there is a reasonable probability that use or exposure will cause serious adverse consequences or death. Moreover, from January 2004 through December 2012, 51% of recalled products were dietary supplements that were adulterated by unapproved drugs.

Efficacy

Claims for the efficacy of plant extracts are based on their long history of use, and on older clinical trials funded by manufacturers. Systematic reviews and meta‐analyses of those trials concluded that they were uninterpretable because of defects in design and interpretation, and publication bias. Rigorous clinical trials supported by the National Institute of Health have found no benefit beyond a placebo effect for a number of popular herbals and supplements, including Echinacea, ginkgo biloba, ginseng, black cohosh, isoflavones, saw palmetto, and glucosamine. Although some medications currently in use were originally identified in plant extracts, the vast majority of herbals have not been evaluated in clinical trials. Their perceived efficacy is based on traditional teaching and on placebo effects.

Conclusions

A fundamental question has been overlooked in recent articles about the quality of plant extracts: Is there any reason to take herbals? Their marketing is based primarily on the unfounded claims that they are safe and effective. Their only potential advantages - lower costs and the convenience of avoiding medical appointments - are outweighed by their hazards and uncertain efficacy.

Herbals and other medicinal products that were designated as supplements by DSHEA should be regulated as medicines. That would require revision or repeal of DSHEA, which is arguably the worst health care legislative act of the twentieth century. Although efforts to amend DSHEA have been blocked by influential congressmen who supported its passage, they should be continued. However, the immediate need is to provide better information to the public. Most supplements are self‐prescribed, and people use them based on misleading information on the Internet and in the media. Health professionals need to communicate more effectively to patients and to the public that there is no reason to consume products whose benefits are unknown and whose risks are evident.

Number of times cited according to CrossRef: 37

Donald M. Marcus, Alternative therapies in academic medical centers compromise evidence-based patient care, Journal of Clinical Investigation, 10.1172/JCI137561,

The Impact of Natural Product Dietary Supplements on Patients with Gout: A Systematic Review and Meta-Analysis of Randomized Controlled Trials, Evidence-Based Complementary and Alternative Medicine, 10.1155/2020/7976130, (1-10), 2020,

Nutritional and medical food therapies for diabetic retinopathy, Eye and Vision, 10.1186/s40662-020-00199-y, 1, 7,

What are the beliefs and behaviours related to sport nutrition supplements, particularly regarding UAE regulatory issues, among male fitness centre members in Dubai?, Clinical Epidemiology and Global Health, 10.1016/j.cegh.2020.02.027,

Suspected‐target and non‐targeted screenings of phosphodiesterase 5 inhibitors in herbal remedies using liquid chromatography-quadrupole time‐of‐flight-mass spectrometry, Drug Testing and Analysis, 10.1002/dta.2861, 0, 0,

Magdalena Ratajczak, Dorota Kaminska, Agata Światły-Błaszkiewicz, Jan Matysiak, Quality of Dietary Supplements Containing Plant-Derived Ingredients Reconsidered by Microbiological Approach, International Journal of Environmental Research and Public Health, 10.3390/ijerph17186837, 18, (6837), 17,

Prevalence and Use of Dietary Supplements Among Pharmacy Students in Saudi Arabia
, Risk Management and Healthcare Policy, 10.2147/RMHP.S256656, (1523-1531), Volume 13,

Fluorescence polarisation for high‐throughput screening of adulterated food products via phosphodiesterase 5 inhibition assay, Drug Testing and Analysis, 10.1002/dta.2926, 0, 0,

Testosterone Imposters: An Analysis of Popular Online Testosterone Boosting Supplements, The Journal of Sexual Medicine, 10.1016/j.jsxm.2018.12.008, 2, (203-212), 16,

Armando E. González-Stuart, José O. Rivera, Herbal Weight Loss Supplements, Dietary Interventions in Liver Disease, 10.1016/B978-0-12-814466-4.00014-8, (175-181),

Amitava Dasgupta, Effects of herbal supplements on clinical laboratory test results, Accurate Results in the Clinical Laboratory, 10.1016/B978-0-12-813776-5.00018-2, (295-318),

Susanna B. Mierau, Ann M. Neumeyer, Metabolic interventions in Autism Spectrum Disorder, Neurobiology of Disease, 10.1016/j.nbd.2019.104544, (104544),

Jozaa Z. AlTamimi, Awareness of the Consumption of Dietary Supplements among Students in a University in Saudi Arabia, Journal of Nutrition and Metabolism, 10.1155/2019/4641768, (1-10), 2019,

Bart I. Roman, Essay: Avoiding unfounded health claims on small molecules in scientific literature, Bioorganic Chemistry, 10.1016/j.bioorg.2019.02.002,

Amitava Dasgupta, Antiinflammatory Herbal Supplements, Translational Inflammation, 10.1016/B978-0-12-813832-8.00004-2, (69-91),

Chemical Barcoding: A Nuclear-Magnetic-Resonance-Based Approach To Ensure the Quality and Safety of Natural Ingredients, Journal of Agricultural and Food Chemistry, 10.1021/acs.jafc.9b01066,

Kelly A. Shipkowski, Joseph M. Betz, Linda S. Birnbaum, John R. Bucher, Paul M. Coates, D. Craig Hopp, Duffy MacKay, Hellen Oketch-Rabah, Nigel J. Walker, Cara Welch, Cynthia V. Rider, Naturally complex: Perspectives and challenges associated with Botanical Dietary Supplement Safety assessment, Food and Chemical Toxicology, 10.1016/j.fct.2018.04.007, (963-971), 118,

Akram Ghasemi Dastjerdi, Maryam Akhgari, Artin Kamali, Zahra Mousavi, Principal component analysis of synthetic adulterants in herbal supplements advertised as weight loss drugs, Complementary Therapies in Clinical Practice, 10.1016/j.ctcp.2018.03.007, (236-241), 31,

Analysis of Pharmacologic Adulteration in Dietary Supplements by Capillary Zone Electrophoresis Using Simultaneous Contactless Conductivity and UV Detection, Chromatographia, 10.1007/s10337-018-3496-2, 4, (689-698), 81,

Isolation and Analysis of Antioxidant Phytochemicals from Black Chokeberry, Maqui, and Goji Berry Dietary Supplements, Advances in Plant Phenolics: From Chemistry to Human Health, 10.1021/bk-2018-1286.ch001, (3-19),

Over-the-Counter "Adrenal Support" Supplements Contain Thyroid and Steroid-Based Adrenal Hormones, Mayo Clinic Proceedings, 10.1016/j.mayocp.2017.10.019, 3, (284-290), 93,

Herbal Dietary Supplements for Erectile Dysfunction: A Systematic Review and Meta-Analysis, Drugs, 10.1007/s40265-018-0897-3, 6, (643-673), 78,

Armando González-Stuart, José O. Rivera, Yellow Oleander Seed, or "Codo de Fraile" ( Thevetia spp.): A Review of Its Potential Toxicity as a Purported Weight-Loss Supplement , Journal of Dietary Supplements, 10.1080/19390211.2017.1353565, 3, (352-364), 15,

Sidney J. Stohs, Harry G. Preuss, What Health Care Professionals Should Know about the Regulation and Safety of Dietary Supplements, Journal of the American College of Nutrition, 10.1080/07315724.2016.1275065, 4, (306-309), 36,

Bill J Gurley, John S Markowitz, David Keith Williams, Gary W Barone, Practical considerations when designing and conducting clinical pharmacokinetic herb-drug interaction studies, International Journal of Pharmacokinetics, 10.4155/ipk-2016-0009, 1, (57-69), 2,

Piotr Rzymski, Monika Jaśkiewicz, Microalgal food supplements from the perspective of Polish consumers: patterns of use, adverse events, and beneficial effects, Journal of Applied Phycology, 10.1007/s10811-017-1079-5, 4, (1841-1850), 29,

Bryan E. Denham, When contaminated dietary supplements cause positive drug tests: methylhexaneamine as a doping agent in sport, International Journal of Sport Policy and Politics, 10.1080/19406940.2017.1348963, 4, (677-689), 9,

Neilson M. Mathews, Prohibited Contaminants in Dietary Supplements, Sports Health: A Multidisciplinary Approach, 10.1177/1941738117727736, (194173811772773),

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Dietary supplements: What's in a name? What's in the bottle?

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The Dietary Supplement Health and Education Act of 1994 (DSHEA), which arbitrarily classified herbals and other medicinal products as dietary supplements, obscured fundamental differences between two classes of products. Authentic supplements to the diet, such as multivitamins or calcium, have nutritional value and are safe.

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Post #4 Red Flag: Red Herring: (Comic Strip)

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Post #4 Red Flag: Red Herring: (Comic Strip)

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Definition: A Red Herring is when someone throws irrelevant distractions into their conversation or argument to distract you from the real topic at hand.  It diverts you from following a logical line of evidence. They seem to have relevance but they do not, in any way, address the discussion point (Ex: 9/11 was a tragic event Response: 9/11 was an inside job. How? They had insurance on the buildings so they did it. response: but who was flying the plane)

Connection: (press photo to make it bigger) In this comic strip Calvin distracts his dad from the real issue at hand. The real issue is Calvin did not listen to instructions about playing ball  in the backyard so he got his ball stuck in the gutters again. To get his dad to agree with getting the ball from the gutter Calvin throws in some red herrings. Calvin says "well at least I'm not embezzling money, I'm not stealing or killing anyone." Calvin's argument is not valid to the real topic at hand, the issue is he is not listening to his father.

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Post #5 Red Flag: Ancient Wisdom (Photo & Article)

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Post #5 Red Flag: Ancient Wisdom (Photo & Article)

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Definition: Ancient Wisdom is the belief that people from the past had a better understanding on the topic at hand. Ancient wisdom is often seen in "alternative"  medical therapies. However, it is illogical to think that ancient people had a better understanding than modern science. Modern science is based of of experiments and evidence while Ancient Wisdom does not have any base or evidences.

Connection: In 2012 the world was preparing for "The End." They believed the Mayan Calendar was the truth to our existence and because it ended in 2012 that must mean the ancients knew something we did not.  This created wide spread hysteria and the term 2012 Phenomenon was coined. This shows that people will put their faith into the hands of people who did not know as much as we do now just because they have "wisdom". https://www.timeanddate.com/calendar/mayan.html

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Post #6 Red Flag: Confirmation Bias (video)

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Post #6 Red Flag: Confirmation Bias (video)

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Definition: Confirmation Bias is our ability/tendency to recall events that take place that coincide with our opinions, and our beliefs. For example, many healthcare workers believe that the full moon indicates a 'crazy' night. They recall these events because it confirms their belief that a full moon essentially leads to a crazy night. On the days that there isn't a full moon, healthcare workers are less likely to remember the events that took place.

Connection: This video relates to confirmation bias because the priest believed that God saved the Athiest (in the red shirt) from the blizzard; when really, a couple of Eskimos helped him. The priest grew up with the facts of God in his life, therefore, he believes that God is the solution to everything. The Athiest on the other hand, grew up in a family that used science as facts. When the Athiest tried to pray to God to help save him, it didn't work. Based on this fact that the Athiest prayed to God, the priest believed that the Athiest now believed in God; but the Athiest responded back with "that's not how it went" (to make sure his point was made), and explained that he was saved by the Eskimos. Our mind constantly searches for information that proves that our perspective/opinion is correct.

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Post #7 Reasons for Belief: Simplicity (website)

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Post #7 Reasons for Belief: Simplicity (website)

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Definition: Simplicity is based on recurring events that take place throughout our lives that may be hard to understand. For example, you have a dream that someone you know is sick, and then you find out that the person you dreamt about is actually sick. People base these events on the simplest answer. They believe that they have psychic abilities, when really, it was just a coincidence.

Connection: This website is an example of simplicity because it shows the coincidence of the events between Abraham Lincoln and John F. Kennedy. The common similarity among both presidents is that each similar event took place 100 years apart (ex. Abraham was elected into Congress in 1846, and Kennedy was elected into Congress in 1946). This could also relate to the unexplained reason for belief because no one can explain the coincidence that happened among all events.

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Simplicity, Complexity, Unexpectedness, Cognition, Probability, Information

by Jean-Louis Dessalles (created 31 December 2008, updated November 2017)

The famous parallel between Abraham Lincoln and John F. Kennedy's fates leaves no one indifferent, even if one knows that the coincidence should not be regarded as unlikely (Kern & Brow, 2001).

"LINCOLN was elected to Congress in 1846, KENNEDY was elected to Congress in 1946."

"LINCOLN was elected president in 1860, KENNEDY was elected president in 1960."

"Both presidents were shot in the head in presence of their wives."

"Both successors were named JOHNSON, born in 1808 and 1908."

"Both assassins were assassinated before being tried."

"BOOTH ran from a theater and was caught in a warehouse,
OSWALD ran from a warehouse and was caught in a theater."

"LINCOLN had a secretary named KENNEDY, and KENNEDY had a secretary named LINCOLN." (false)

"KENNEDY was shot in a car named LINCOLN"

. . .

These coincidences should not be considered an objective marvel (Kern & Brown, 2001). However, the fact that it holds a fascination for most of us reveals that some systematic cognitive phenomenon is at work, and this demands an explanation. Let's list a few factors that are crucial in the Lincoln-Kennedy example.

1. Analogy: Each common feature between Lincoln and Kennedy's lives adds to the coincidence. The repeated 100-year interval in the two-president coincidence is an analogy within the analogy.

2. Association: Non-analogue features, such as the fact that Kennedy was shot in a car named Lincoln, still add to the value of the coincidence.

3. Prominence: Kennedy and Lincoln are among the foremost US presidents. The coincidence would be less interesting if it involved obscure US presidents, or prominent Uruguayan presidents (for non-Uruguayan citizens).

4. Round numbers: The Lincoln-Kennedy coincidence would be less interesting if it involved an 87-year interval.

All these parameters have a systematic influence on the perception of coincidences. This is an indication that some genuine cognitive competence is at work and that the surprise generated by coincidences is not a mere side-effect of some general sensitivity to the presence of statistical exceptions. Probabilistic or statistical accounts would fail to account for the above properties.
Simplicity Theory explains the influence of all these factors (Dessalles 2008a).

By definition, unexpectedness U is the difference between generation complexity and description complexity: C w - C. Let's compute both terms.

Let's call s ₁ and s ₂ the two terms of the coincidence. If we make the crucial hypothesis that the two events areindependent, the " W-machine" has to do the work twice to generate the two events together, s ₁ & s ₁:

The " O-machine" requires the following complexity:

U(s ₁ & s ₂)> C w(s ₁) + C w(s ₂) - C(s ₁) - C(s ₂|s ₁) (1)

If both events are of comparable complexity: C(s ₁) ≈ C(s ₂) and are not unexpected separately: C w(s ₁) ≈ C(s ₁), we get:

This expression predicts all aspects of coincidences.

1. Analogy: It correctly predicts the importance of a close analogy between the two events, as best analogies make C(s ₁ & s ₂) minimum (Cornuéjols, 1996; Murena et al., 2017). Each new common element, such as the birth date of the successors in the Lincoln-Kennedy parallel, has to be generated twice by the W-machine, but only once by the O-machine. Its impact on the conditional complexity C(s ₂|s ₁) is zero. Common elements thus add to the unexpectedness of the situation. An additional prediction is that more complex common elements will add to unexpectedness (e.g. if both presidents had been besides their secretary of defence's spouse when they were shot).

2. Association: Expression (2) above predicts that any element of s ₁ that the O-machine can reuse to generate s ₂ will add to the surprise. Hence the mention that Kennedy was killed in car named 'Lincoln'. The W-machine must generate the make of the car and requires several bits which add to C w(s ₂) to distinguish it from other makes; this generation is easier for the O-machine when s ₁ is given as input, as the name 'Lincoln' is available for free.

3. Prominence: Why is it important that Abraham Lincoln and John F. Kennedy be famous? Expression (1) above provides an answer. These two persons exist and are unique in the subject's world; the W-machine has thus no work to do to generate them. For the O-machine, however, their minimal description may go through determining their social role, US president, and then find them in a ranked list of US-presidents. Hence the importance for the coincidence to involve two prominent figures, as their lower complexity, which amounts to the logarithm of their rank in a list ordered by celebrity, diminishes both C(s ₁) and C(s ₂|s ₁) in expression (1) above, and thus adds to unexpectedness. Conversely, a social role such as president of Uruguay, if more complex for the observer, would make the coincidence less surprising, as it would significantly add to C(s ₁) and to C(s ₂|s ₁).

4. Round numbers: The presence of the negative term -C(s ₂|s ₁) in the expression of unexpectedness explains why the Lincoln-Kennedy story is more interesting as it is, rather than if the repeated time interval had been of 87 years instead of 100. The point is that the cognitive complexity of the program that transforms 1846 into 1946 or 1860 into 1960 is simpler than the program that would transform 1846 into 1933 and 1860 into 1947 (the first program affects only one digit). Alternatively, one can observe that 100, as a number, is simpler than 87. The complexity of an integer n is not larger than log₂ n. In the case of round numbers, it is significantly smaller. One million may be concisely defined as 10⁶, or as 1 followed by six copies of 0.

The above considerations generalize to any coincidence. Interestingly, proximity effects apply to coincidences, not only for egocentric distances, but also for allocentric distances (i.e. distances between s ₁ and s ₂ in time, space, social networks, ...) as C( s ₂|s ₁) crucially depend on them.

Cornuéjols, A. (1996). Analogie, principe d'économie et complexité algorithmique. Actes des 11èmes Journées Françaises de l'Apprentissage. Sète: .

Dessalles, J.-L. (2007). Spontaneous assessment of complexity in the selection of events. Technical Report ParisTech-ENST 2007D011.

Dessalles, J.-L. (2008). Coincidences and the encounter problem: A formal account. In B. C. Love, K. McRae & V. M. Sloutsky (Eds.), Proceedings of the 30th Annual Conference of the Cognitive Science Society, 2134-2139. Austin, TX: Cognitive Science Society.

Dessalles, J.-L. (2008). La pertinence et ses origines cognitives - Nouvelles théories. Paris: Hermes-Science Publications.

Kern, K. & Brown, K. (2001). Using the list of creepy coincidences as an educational opportunity. The history teacher, 34 (4), 531-536.

Murena, P.-A., Dessalles, J.-L. & Cornuéjols, A. (2017). A complexity based approach for solving Hofstadter's analogies. In A. Sanchez-Ruiz & A. Kofod-Petersen (Eds.), International Conference on Case-Based Reasoning (ICCBR 2017), 53-62. Trondheim, Norway: .

Warren, C. N. (1934). Modern news reporting. New York: Harper & Brothers, ed. 1959.

Back to the Simplicity Theory page.

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Simplicity, Complexity, Unexpectedness, Cognition, Probability, Information by Jean-Louis Dessalles (created 31 December 2008, updated November 2017) The famous parallel between Abraham Lincoln and John F. Kennedy's fates leaves no one indifferent, even if one knows that the coincidence should not be regarded as unlikely (Kern & Brow, 2001).

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Post #8 Reasons for Belief: Agenticity (video)

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Post #8 Reasons for Belief: Agenticity (video)

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Definition: Agenticity is the belief of invisible beings (agents) that have some impact on their lives. People will naturally assign meaning or intention to these invisible beings. People make up meanings to what has happened to them to understand better which has created these entities. Spirits, Gods, Angels, Aliens and Government Conspirators are all examples of invisible agents that can have power and are believed to control our lives.

Connection: In this video we look at some creation stories. Nearly all of them start with the idea of nothingness and then an invisible being creates all that we have on earth now. Creation myths were made because humans have a natural desire to know what happened, and when there is no easy explanation they make one. The idea of an invisible being or a god creating the Earth is synonymous through many cultures.

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Creation from the Void: Crash Course World Mythology #2

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Post #9 Reasons for Belief: Patternicity (video)

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Post #9 Reasons for Belief: Patternicity (video)

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Definition: Patternicity (also called Apophenia) is the ability to see meaningful patterns in everyday objects (even when the patterns don't exist). An example of this is looking at the clouds, and seeing a person, or a face.

Connection: In this video, Savage talks about the human  capability of inventing "something out of nothing." He claims that when we see patterns in objects (that are completely unrelated), it's our minds acting as a "survival mechanism" (https://www.youtube.com/watch?v=eu_Z5iZ_NN8&t=40s) to identify these patterns.

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Post #10 Critical Analysis: All-Natural Supplements (article)

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Post #10 Critical Analysis: All-Natural Supplements (article)

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Define Problem: The extraordinary claim is that dietary supplements can cure the COVID-19 virus.

Gather Evidence: This article is based on the effects of vitamin C, vitamin D, zinc, elderberry, and silver supplements against the COVID-19 virus. Pharmacists believe that these supplements may not cure the COVID-19 virus, however, it may help manage the virus among patients (not recommended to use these supplements for self-treatment).

Evaluate Evidence: This article was published by medical professionals, (pharmacists to be more accurate.) This journal is peer reviewed and accurately cited by the authors. This journal has a DOI number which also proves it authenticity. When cross referenced it shows that their claims are accurate. According to( Michenizi, S.M. July 22,2020. Can vitamins and/or supplements provide hope against coronavirus?.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7313552/ ) the coronavirus cannot be cured or supplemented by vitamins or traditional Chinese medicines however, they can help ease the symptoms of the virus. This article is also a medical journal and peer reviewed. This further proves the validity of the original Journal Myth Busters: Dietary Supplements and Covid-19.

Recognize Assumptions: The medical professionals are striving to find anything to help patients. They will look into vitamins and supplements naturally as it is known some anti-inflammatory supplements show some promise in helping inflammation. It is the job of these scientists and pharmacist to keep the population safe and if some are already trying to remedy with supplements it is their responsibility to test out these claims and bring accurate information to the public. Potentially someone may read these articles at a glance and assume they should be taking these vitamins and supplements in replacement for medical advice. These articles took this into consideration by starting the journal off with a disclaimer stating, " Patients should not rely on dietary supplements to prevent or treat COVID-19. " and, "...the role of the pharmacist is essential. Here, we review theoretical mechanisms and evidence related to efficacy and safety of select supplements in the setting of COVID-19."

Synthesize Evidence: (If the consumer chooses to use the supplements-for a sense of security), the pharmacists should educate these consumers about the 'potential risks' that these supplements may cause. Other solutions to prevent the spread of the COVID-19 virus consist of: avoiding exposure with people who have come in contact with the virus, sanitizing/disinfecting surfaces, using hand-washing practices, wearing a mask, maintaining social distance, and following basic safety precautions that the government has put into place.

Select Best Alternative: Ultimately, the best choice that you can make in order to keep yourself/others safe from the virus, is to follow the safety precautions that have been put into place. The reason for this is because you don't always know what chemicals are being put into these supplements- which could cause greater damage to your body. There is not always a sure way through the FDA and Health Canada to regulate the amount of vitamin in the capsules. Although these supplements may seem helpful to some people, society has a greater chance at surviving the pandemic if everyone follows the rules.

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Abstract

News and social media platforms have implicated dietary supplements in the treatment and prevention of coronavirus disease 2019 (COVID-19). During this pandemic when information quickly evolves in the presence of contradicting messages and misinformation, the role of the pharmacist is essential. Here, we review theoretical mechanisms and evidence related to efficacy and safety of select supplements in the setting of COVID-19, including vitamin C, vitamin D, zinc, elderberry, and silver. Evidence evaluating these supplements in COVID-19 patients is lacking, and providers and patients should not rely on dietary supplements to prevent or treat COVID-19. Rather, reference to evidence-based guidelines should guide treatment decisions.

Background

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 (COVID-19) pandemic gripping the globe in 2020.1 During this difficult time, when health care systems and providers are constantly strained, the public is more likely to seek medical information from online sources. Prominent medical entertainment personalities have been featured on television programs and across social media platforms touting the use of certain dietary supplements to both protect individuals from contracting COVID-19 and aid in its acute treatment. In fact, sales of dietary supplements such as elderberry and zinc have significantly increased by as much as 255% and 415%, respectively, in the single-week period ending March 8, 2020.2 The US Food and Drug Administration (FDA) actively monitors for false marketing claims and has issued warning letters to multiple companies selling products with false claims for prevention and treatment of COVID-19, but more needs to be done.3 It is paramount that pharmacists, who are often on the front lines of this pandemic, be aware of the data supporting or refuting dietary supplement use to help patients make informed decisions during this time of information overload and confusion. Here, we review select supplements that have been most frequently touted within social media and news outlets for COVID-19 prevention and/or treatment, including vitamin C, vitamin D, zinc, elderberry, and silver.

Vitamin C

Vitamin C (ie, ascorbic acid) has several physiological properties that make it an attractive option to both prevent viral infections and treat the resulting severe illness. These include, but are not limited to, scavenging oxygen free radicals, decreasing the gene expression of proinflammatory cytokines, and enhancing microbial killing in certain cell types.4,5 Despite these theoretical benefits, evidence does not support the routine use of vitamin C for prevention of viral infections, including the common cold.6 Meta-analyses of clinical trial data does suggest a shortening in common cold duration by a modest 8% with regular vitamin C intake (amounts varying across studies).6 Whereas the common cold can be caused by a human coronavirus, COVID-19 is caused by a novel coronavirus with a different genome sequence.7 It cannot be assumed, therefore, that outcomes of vitamin C from the management of the common cold will translate to the management of COVID-19.

Some of the distinguishing features of a more severe COVID-19 infection course include development of acute respiratory distress syndrome (ARDS), secondary infection (eg, bacterial pneumonia), and severe sepsis.7 Recently published clinical trials have investigated vitamin C use as part of a management strategy for ARDS8 and septic shock.9 The CITRIS-ALI trial showed that giving intravenous (IV) vitamin C 50 mg/kg every 6 hours for 96 hours did not significantly alter disease severity scores, C-reactive protein levels, or thrombomodulin levels compared with placebo in patients with sepsis and ARDS, although 28-day all-cause mortality was significantly lowered and ICU-free days was significantly shorter with vitamin C use.8 Similarly, the VITAMINS trial showed that a combination of IV vitamin C, hydrocortisone, and thiamine did not improve duration of time alive or free from vasopressor administration compared with hydrocortisone alone in a population with septic shock.9

Physicians from China have stated on various media outlets that they have successfully treated more than 50 patients with moderate to severe COVID-19 with large doses of IV vitamin C (10 000-20 000 mg/d), leading to a shorter mean hospital length of stay compared with untreated patients with COVID-19 and no incidences of death.10 Details of this evidence are unavailable because these findings have not (at the time of this writing) been published in either preprint or peer-reviewed journals. It is also important to note that the high doses used in this study are not obtainable when using orally available over-the-counter versions of vitamin C. Moreover, the gastrointestinal adverse events (nausea, vomiting, heartburn, abdominal cramps) could be dose limiting, and pharmacists should advise patients against attempting to take that much daily supplement. High doses of vitamin C may be associated with formation of kidney stones, particularly in those with high oxalate levels to begin with.11 Randomized controlled trials of vitamin C are currently registered on the National Institutes of Health ClinicalTrials.gov website examining monotherapy (NCT04264533, NCT04344184, NCT03680274, NCT04357782) for acute COVID-19 treatment, in combination with hydroxychloroquine to treat (NCT04328961) or prevent (NCT04326725, NCT04335084) COVID-19 and with other supplements for prevention (NCT04342728). The dosing of vitamin C in these trials varies widely, ranging from 250 to 500 mg orally daily to 24 g IV daily. Overall, it is important for pharmacists to highlight the lack of evidence that vitamin C can be taken to prevent or treat COVID-19. Instead, patients should consult with trusted resources ( Table 1) or their physician regarding the most effective way to avoid COVID-19.

Evidence-Based Resources for COVID-19 and Dietary Supplements.

Vitamin D

Vitamin D is a fat-soluble vitamin and is found in supplements and foods as vitamin D ₂ (ergocalciferol) and D ₃ (cholecalciferol), both of which require further metabolism into the active form, calcitriol.12 Vitamin D is the proposed driver of the "seasonal stimulus" hypothesis that emerged from epidemiological observations of the influenza A epidemics.13 This idea suggests that coinciding with peak influenza cases in the winter is a reduced exposure to the sun, leading to reduced synthesis and serum levels of vitamin D, which in turn affects immune function.13 The complex mechanisms by which vitamin D supports immune function have been reviewed extensively.13-16 To summarize, vitamin D activity contributes to the maintenance of cell physical barrier integrity, enhanced antimicrobial peptide expression, enhanced activity of our innate immunity through macrophages and monocytes, and shifting response of cells involved with innate and adaptive immunity, such as dendritic and T-cells, toward a more tolerable and anti-inflammatory behavior.

Observational data consistently associate low vitamin D levels with acute respiratory tract infections.17 Patients may also be at risk of ARDS with low vitamin D levels.18 Trial evidence is less consistent, perhaps because of heterogeneity in baseline vitamin D levels or the regimens studied.13,19 The largest evaluation to date, an individual patient data meta-analysis, included more than 10 000 individuals from 25 high-quality trials.19 Investigators concluded that oral vitamin D ₃ supplementation reduced the risk of acute respiratory tract infections (number needed to treat [NNT] = 33; range = 20 to 101). Effects were stronger when baseline 25-hydroxyvitamin D levels were <25 nmol/L (NNT = 8; range = 5 to 21) and with daily (vitamin D ₃ oral doses ranging from 400 to 4000 IU) or weekly dosing versus regimens with bolus doses. No signals of serious adverse events were identified; renal stones (0.2%) and hypercalcemia (0.5%) were rare overall and balanced between treatment arms.19

This prior knowledge currently underlies internet reports speculating a role for vitamin D in the COVID-19 pandemic. The former director of the Centers for Disease Control and Prevention (CDC)20 and faculty from the University of Turin in Italy have both suggested that ensuring adequate vitamin D levels through safe sun exposure, food, or vitamin D supplementation may have a role in COVID-19 management.21 The report from Italy takes it further to suggest a possible role of IV calcitriol in patients with COVID-19 and compromised respiratory function and claims a "very high prevalence of hypovitaminosis D" in patients with COVID-19 in Turin. Data were not published at the time of writing this review. A single sample of 20 patients hospitalized with COVID-19 and with available vitamin D levels suggests that vitamin D insufficiency is prevalent.22 Ongoing studies aim to evaluate the relationship between vitamin D levels and prognosis in patients with COVID-19 as well as efficacy of vitamin D supplementation as part of treatment.23,24

Without studies specific to COVID-19, whether taking daily vitamin D improves outcomes associated with COVID-19 is unknown. For the purpose of overall general health and in the setting of a high prevalence of vitamin D deficiency in America,25 patients should continue to follow recommendations for daily vitamin D consumption consistent with the recommended daily allowance and tolerable upper intake level. For adults, this is within the range of 600 or 800 IU to 4000 IU.12 Until scientific evidence emerges, patients should avoid excessive doses of vitamin D in hopes of preventing or treating COVID-19. Long-term consumption of vitamin D in excess of 4000 IU is considered possibly unsafe and could lead to hypercalcemia.26

Zinc

Zinc is a trace mineral that has been hypothesized to inhibit viral replication and attachment to the nasopharyngeal mucous, and through this mechanism, has been implicated in the management of the common cold.27,28 In vitro studies suggest that zinc modifies effects of several respiratory pathogens, including rhinovirus, respiratory syncytial virus, and SARS-COV.

Results from clinical trials evaluating zinc supplements for the common cold have conflicted, and many suffer from methodological flaws.28 Similarly, conclusions of multiple meta-analyses vary in whether zinc significantly affects cold duration and to what extent patient and regimen characteristics modify treatment effects.32-35 One comprehensive systematic review with broad inclusion of studies found moderate quality evidence that zinc supplementation reduces common cold duration by 1.65 days.32 Considerable heterogeneity was found and partially explained by age, zinc dose, and salt form. Adverse events were more common with zinc compared with placebo.

News reports are starting to emerge with claims that zinc may have a role in COVID-19 management, and this may be a result of prior knowledge that some coronaviruses can cause the common cold. A physician in New York is claiming to have near perfect clinical response to prescribing his patients a combination of hydroxychloroquine, azithromycin, and zinc, although data supporting these claims have not been published.39

There are no studies evaluating zinc for COVID-19 management to date, although a few trials are currently registered to test zinc as part of a regimen to treat COVID-19.40 Some patients may choose to take zinc during this pandemic, but reputable data are lacking. Oral zinc supplementation is likely to be safe up to 40 mg/d in adults, but safety is less certain with greater doses that are implicated in common cold management.41 Adverse effects include, but are not limited, to nausea, vomiting, and changes in taste. The nasal preparation should not be used because of reports of the permanent loss of the sense of smell.

Elderberry

Elderberry ( Sambucus nigra) is hypothesized to have antiviral properties because of its ability to modulate inflammatory cytokines42 and has been tested both in vitro43-47 and in vivo against varying viruses.48-52 At the time of writing, there are no published studies evaluating the use of elderberry and COVID-19. Although elderberry and its phenolic acid components exhibit antiviral activity against human coronavirus HCoV-NL63 in vitro,44 this cannot be extrapolated to COVID-19 as previously mentioned.7

Randomized, double-blind, placebo-controlled trials evaluating elderberry for treatment of influenza have suggested that elderberry may reduce symptom duration. The utility of these findings is unclear because of the small sample size, lack of objective outcomes, omission of intention-to-treat analysis, and lack of adverse event reporting. The trials do not align with standard of care because patients who received the annual influenza vaccine were excluded. In these trials, 1 tablespoon of elderberry oral solution was administered 4 times daily for 3 to 5 days within 24 to 48 hours of initial symptoms.48,49 Elderberry 175-mg lozenges were administered 4 times daily for 2 days within 24 hours of symptoms.50

The results of a randomized, double-blind, placebo-controlled trial evaluating elderberry in air travelers suggested that elderberry may reduce cold symptom duration and severity.51 Elderberry capsules were initiated at 600 mg daily 10 days prior to travel. One day prior to travel, the dose was increased to 900 mg daily and continued for 4 to 5 days after arrival.51 Patients with chronic respiratory diseases such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis were excluded. Half of the participants reported using additional symptom-relief medications for an average of 1.5 days during the trial, limiting the application of these findings.51

Elderberry is likely safe when cooked and consumed in moderation.42 It is dangerous to consume uncooked elderberry, bark, root, leaves, and unripe berries because of the risk of cyanide toxicity.42 Elderberry should be used with caution in patients with diabetes because of its ability to stimulate insulin and promote glucose metabolism.42 Other potential adverse effects of elderberry include nausea, vomiting, diarrhea, tachycardia, hypotension, hypokalemia, and dehydration resulting from diuresis.38 Elderberry may have the ability to stimulate cytokines53 and, thus, may interfere with immunosuppressant therapy. Additionally, elderberry may alter theophylline levels.42

Although there exists a hypothetical benefit of elderberry for the treatment of viral infections, conclusive evidence from high-quality clinical trials is lacking, and data addressing elderberry's role with COVID-19 are absent.

Silver

Colloidal silver has been used for medicinal purposes throughout history because of its proposed antibacterial54 and antiviral properties.55,56 Colloidal silver describes silver particles suspended in liquid.57 It is heavily marketed despite discouraging safety and efficacy data.58,59 Silver toothpaste and silver solution were recently promoted by social media personalities as potential cures for COVID-19.60,61

In 1999, the FDA declared that over-the-counter products containing silver were not recognized as safe or effective and that any colloidal silver product marketed for a medical purpose was misbranded.59 Extensively documented in the literature, the most common side effect of silver exposure is argyria, an irreversible gray or blue-gray skin discoloration. Systemic silver exposure may have additional harmful effects on the gastrointestinal system, liver, kidney, and other major organs.62 Long-term ingestion of silver has resulted in reports of neurotoxicity, seizure, acute psychosis, acute myeloid leukemia,63 and leukocytoclastic vasculitis.64

Despite the FDA's warning, colloidal silver is still readily available and advertised to the public.58,59 Until new evidence supports safety and efficacy, patients should not consume over-the-counter colloidal silver products.

Viewpoint

Pharmacists are an accessible drug information resource who have the ability to provide real-time data-driven education to patients and providers. News and social media reports should not be the sole source for evidence-based information. During this pandemic when information quickly evolves in the presence of contradicting messages and misinformation, the role of the pharmacist is essential.

Patients and providers should not rely on dietary supplements to prevent or cure COVID-19.65 Current guidelines for the treatment of COVID-19 do not comment on dietary supplements and, currently, do not recommend any pharmacological interventions widely with the exception of use through clinical trials. Pharmacists have the responsibility to ensure that patients have accurate information regarding the current lack of data supporting efficacy of these supplements in COVID-19. On the other hand, patients may choose to self-treat with these supplements because they are easily accessible and may provide a sense of security. This practice can be dangerous as seen in the death of a man who ingested chloroquine phosphate, a fish tank cleaner, to prevent COVID-19.69 In these cases, pharmacists have the responsibility to ensure patient safety regardless of whether they agree with the patient's choice to self-treat. This is possible by screening for contraindications and drug or disease state interactions that are known to exist for the specific dietary supplement. In addition, pharmacists should educate patients on the potential harms and monitoring parameters known for these supplements. Resources such as the Natural Medicine Database or the National Institute of Health Office of Dietary Supplements website provide clinician- and consumer-directed information that is evidence based.70

The best method to prevent spread of COVID-19 is to avoid being exposed.71 Currently, the CDC recommends to avoid touching the face with unwashed hands, wearing a cloth face cover over the nose and mouth in public, and covering the mouth and nose when coughing or sneezing.71 It is recommended to wash hands with soap and water for at least 20 s to prevent transmission.71 When soap and water are unavailable, hand sanitizer containing at least 60% alcohol may be used instead.71 The CDC recommends avoiding contact with others who are sick and to practice social distancing measures. Finally, highly touched surfaces should be cleaned and disinfected daily. Patients, providers, and pharmacists should refer to the CDC website for regular updates regarding prevention strategies and recommendations.

Declaration of Conflicting Interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding
The authors received no financial support for the research, authorship, and/or publication of this article.

ORCID iDs
William L. Baker https://orcid.org/0000-0003-2172-0931

Diana M. Sobieraj https://orcid.org/0000-0002-5227-0681

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# data[].attributes.attachment_link.title
Myth Busters: Dietary Supplements and COVID-19 - Kathleen K. Adams, William L. Baker, Diana M. Sobieraj, 2020

# data[].attributes.attachment_link.description
Abstract News and social media platforms have implicated dietary supplements in the treatment and prevention of coronavirus disease 2019 (COVID-19). During this pandemic when information quickly evolves in the presence of contradicting messages and misinformation, the role of the pharmacist is essential.