Chapter 6: Dietary Supplements

By Mary Marian, DCN, RDN, FAND, FASPEN

Introduction

Culinary medicine prioritizes healthy eating patterns that provide adequate energy and essential nutrients from food. Sometimes conditions arise for which dietary supplementation is needed and helpful.

A dietary supplement is a product taken by mouth that is intended to supplement the diet and is labeled as a dietary supplement. Many thousands of supplements are available for purchase. These are promoted for a variety of uses, including improving overall general health and preventing disease(s), treating a current medical issue, promoting weight loss or increased muscle mass, increasing energy, and improving athletic and sexual performance.

Although the US Food and Drug Administration (FDA) has established Good Manufacturing Practices (GMPs) that set expectations for how dietary supplements must be manufactured, prepared, and stored, the safety and efficacy ultimately are left to the manufacturer and can be uncertain. Supplement labels cannot claim to treat, cure, mitigate, or prevent a disease. Still, they can reflect a relationship between a supplement ingredient and the possibility of reducing the risk for a medical issue or a disease, and they may state how a product may affect the body and can make a health claim.

Deceptive advertising is common in the supplement industry. Products labeled “natural” are not necessarily safer and healthier, although consumers often assume this to be true. Adverse side effects have been reported related to ingredients not listed on the label and contaminants.

How the product is used or consumed, the amount consumed, and the individual’s health status can influence tolerance and outcomes. Many supplements are widely used without medical supervision, and many are ineffective related to their intended use. An important concern is that some supplements can alter the efficacy of prescribed medications. Given the prevalence of use and lack of oversight regarding safety and efficacy, it is vital that health-care professionals and consumers be aware of the safety issues associated with dietary supplements and how to determine if a supplement is needed, as well as how to make educated decisions when purchasing these products.

Culinary Medicine and Dietary Supplements

Culinary medicine promotes healthy eating behaviors, focusing on the consumption of a healthy diet primarily composed of a variety of whole and unprocessed foods for disease prevention or disease management. However, food allergies and food preferences, medical conditions, and the lack of access to or costs of various types of foods may warrant a need for dietary supplements.

Dietary supplements, defined in the accompanying text box, are widely used by consumers of all ages, with use continuing to increase.¹ Estimates indicate consumers spend more than $130 billion annually on various types of supplements.²

In the 1990s, prior to the passage of the Dietary Supplement and Health Education Act (DSHEA), about 4,000 different supplements were available. Today, more than 85,000 different supplement types can be purchased in stores and/or online. Reportedly, almost 58% of adults in the United States use dietary supplements, with 63.8% of women reporting using supplements in comparison to 50.8% of men.³ According to Mishra et al., use also increases with aging.³

More than 35% of individuals surveyed reported using 2 or more supplements in the past 30 days. In this survey, the most common types of supplements used were multivitamin/mineral, vitamin D, fish oils, and vitamin C products.³ Other commonly used supplements include botanicals, calcium, and vitamin B₁₂. Reported supplement use increased from 48.4% in 2007 to almost 58% in 2017–2018 for all adults.³ When adjusted by age, 74.3% of adults aged 60 years or older reported taking at least 1 supplement daily, with 24.9% taking 4 or more supplements.

This chapter reviews safety concerns and considerations, efficacy, when to consider supplementation, and guidelines for evaluating supplement use and/or need.

Safety

Dietary supplement products are overseen by the FDA but, unlike pharmaceutical drugs, dietary supplements are not strictly regulated. Enacted in 1994, the DSHEA outlined rules for the labeling and safety of dietary supplements.¹ However, the DSHEA also stated that the “FDA is not authorized to review dietary supplement products for safety and effectiveness before they are marketed,” thereby placing the responsibility for safety on the manufacturers.¹

Products can only be removed from the market after the FDA has proved that a supplement is unsafe.¹ In these instances, the FDA will issue public notifications and press releases to alert the public of safety concerns.

In 2007, the FDA established requirements and guidelines (GMPs) for dietary supplements.⁴ The GMPs set forth expectations by which dietary supplements must be manufactured, prepared, and stored to ensure quality.⁵ Companies are expected to guarantee the identity, purity, strength, and composition of their products.¹ Reporting of serious adverse effects is also mandatory. The FDA must also be notified before products with new dietary ingredients are marketed.

Since January 2011, when the Food Safety Modernization Act was passed, the FDA has had the authority to recall products without relying on the manufacturer to voluntarily remove misbranded or adulterated products from the marketplace.⁵ Furthermore, passage of this act requires manufacturers to verify safety of ingredients used from foreign suppliers, because constituents used in supplements, as well as the supplements themselves, are now manufactured around the world.

Despite these regulatory changes, quality control regarding safety and efficacy are still the responsibility of the manufacturer. Although manufacturers are responsible for producing supplements that are safe, they do not need to establish safety or effectiveness before they are available in the marketplace.

Many supplements are widely used without medical supervision. Moreover, many have been found ineffective related to their intended use.⁶ In fact, the FDA issued a warning for consumers that supplements used for weight loss, increasing muscle mass, and improving sexual function are more likely than other supplements to be deceptively marketed and contain with toxic ingredients.⁷

Dietary Supplement Claims

Drug labels can claim to treat, cure, mitigate, or prevent a disease, but this is prohibited for dietary supplements. Three types of claims are allowed on supplement labels: nutrient content, structure/function claim, and/or a health claim.¹ For instance, a supplement label may reflect a relationship between a supplement ingredient and the possibility of reducing the risk for a medical issue or a disease.

In a structure/function claim, a manufacturer may state how their product would possibly affect the body, but the statement cannot mention any specific medical problem. Products are also required to have a disclaimer that reads, “This statement has not been evaluated by the FDA. This product is not intended to diagnose, treat, cure, or prevent any disease.”¹

Consumers are often drawn to products that are advertised as “natural,” because as they equate the term natural with being healthier and safer. However, this assumption is not correct: a variety of adverse side effects have been reported related to the chemical makeup of products. In addition, some ingredients contained in a product may not be listed on the label, and some products may contain contaminants. How the product is used or consumed, the amount consumed, and the health status of the individual using it are other factors that influence tolerance. The amount and effect of a product ingredient can be dramatically different when consumed as a tea rather than as an extract. Common side effects that have been reported with use of these products include diarrhea, dehydration, nausea, vomiting, electrolyte alterations, cardiac arrhythmias, and liver damage.⁸

Reportedly, the FDA completes approximately 500 inspections of dietary supplements annually.⁹ Products are generally recalled if they are found to be contaminated with medications, microbes, pesticides, and/or heavy metals.^1,9 Information regarding products tainted with contaminants can be found in the FDA’s Health Fraud Product Database.¹⁰ Recalls occur also when product manufacturers make inaccurate claims and/or the product does not contain what the label states regarding amounts (e.g., they may contain too little or too much of a particular ingredient).

An additional concern is that more than 180 dietary supplements can alter the efficacy of a variety of prescribed medications (see Potential Medication-Supplement Interactions text box). For example, herbal supplements such as St. John’s wort can reduce the efficacy of several drugs, including medications for heart disease, depression, HIV/AIDs, and birth control, to name a few.¹¹ Prior to surgery, a variety of dietary supplements should be discontinued, including commonly used products such as turmeric, vitamin E, fish oils, and melatonin because these increase the risk for bleeding. A more in-depth list is available from UCLA Health.¹²

The FDA’s Dietary Supplement Ingredient Directory provides information regarding safety concerns about components found in various supplements.¹³ The text box titled “Herbal Supplements that Should Be Avoided or Used with Caution” reflects current recommendations for avoiding or cautiously using various products.^11,13

When to Consider Supplementation

Consideration for recommending dietary supplements is often required when working with populations at high risk for developing deficiencies. Malnourished patients also often require supplementation to correct deficiencies that are present. Furthermore, individuals who might be considered in overall general good health may present with deficiencies that require supplementation. For example, a healthy individual may be diagnosed with megaloblastic anemia due to a vitamin B₁₂ deficiency after taking a medication such as a proton-pump inhibitor (PPI) for many years, because PPIs reduce B₁₂ absorption.

The “Populations at Risk for Developing Nutrient Deficiencies” text box illustrates additional populations at risk for developing nutrient deficiencies where supplementation may be beneficial.

Completing a comprehensive nutrition assessment is essential for identifying individuals who have or are at high risk for developing nutritional deficiencies that may warrant need for supplementation (see Steps in Completing a Comprehensive Nutrition Assessment text box). Additionally, a nutrition-focused physical exam can help clinicians detect signs of deficiencies if they are present. Evaluating past medical history, current health status, and prescribed medication use provides more data for risk assessment.

Risk for a deficiency based on health status as well as risk for harm if using a supplement is also paramount when evaluating and recommending supplements. For example, probiotics have generally been found to be safe when used by healthy individuals but have also been associated with adverse effects in patients requiring critical care.¹⁴ In addition to eliciting use of prescribed medications, use of all dietary supplements and rationale for use should be obtained. Laboratory data can also be used for confirming if deficiencies are present.

Lastly, completing a thorough evaluation of dietary intake—including eliciting food preferences, allergies, and intolerances—is essential when completing a risk assessment. The ability to purchase and prepare meals provides additional details related to the possibility of developing deficiencies. Moreover, assessing dietary intake in addition to supplement use is necessary to evaluate whether individuals are consuming too little or too much of specific nutrients. Consumers often do not consider that intake of fortified foods in addition to supplement use can result in overconsumption of various nutrients. Although this usually is not a concern, toxic levels of certain vitamins (e.g., pyridoxine [B₆]) can lead to adverse outcomes. Table 6.1 provides details regarding commonly used supplements, doses, and additional information that should be considered.

Table 6.1. Commonly Used Supplements^11-43

	Conditions that may warrant supplementation	Dose	Notes
Vitamins
Thiamin (vitamin B1)	Congestive heart failure, alcohol abuse, malabsorptive disorders, persistent nausea and vomiting	100-500 mg/d	Deficiency can develop in 9-18 days with inadequate intake and/or persistent diarrhea.
Riboflavin (vitamin B2)	Migraine headaches, vegan diet, individuals with lactose intolerance	400 mg/d for migraines; RDA for age and sex	Deficiency is rare.
Niacin (vitamin B3)	Therapeutic doses prescribed to reduce serum cholesterol levels	>500-2,000 mg/d with medical supervision	Adverse effects: flushing, headache, and liver damage.
Folate (vitamin B9)	Female individuals of childbearing age, alcohol abuse, megaloblastic anemia, malabsorptive disorders, and cognitive disorders	Women of child-bearing age: 400-800 mcg/d See RDA for age and sex 1 mg/d for individuals with an alcohol dependence	Trials have not shown improved cognitive function with supplementation. Medications such as sulfasalazine and methotrexate reduce the absorption of folate. Assess for B12 deficiency prior to supplementation.
Vitamin B12	Megaloblastic anemia, medications, bariatric surgery, ostomies, and cognitive disorders	1,000 mcg/d orally or intramuscularly to correct deficiency	Trials have not shown improved cognitive function with supplementation.
Vitamin C	Smokers, wound healing, and colds	Smokers: ≥30 mg/d; individuals with wounds: 500 mg/d	Promotes increased absorption of iron.
Vitamin D	Vitamin D deficiency, malabsorptive syndromes, end-stage renal and liver diseases, limited sun exposure, individuals with darker skin, obesity, malnutrition, some medications and chemotherapy agents	Varies based on vitamin D status; RDA based on age and sex; 50,000 IU/week for 6 weeks when levels < than normal limits	To assess status, measure blood levels of 25-hydroxyl vitamin D. Vitamin D3 is the form of vitamin D recommended for supplementation.
Vitamin E	NAFLD	800 IU/d for NAFLD	Doses >200 IU/d may increase the risk for prostate cancer.
Minerals
Calcium	Bone health, and may reduce the risk for colorectal cancers or colon adenomas	Achieve RDA for age and sex through oral and/or supplementation	500 mg at a time decreases absorption. Calcium carbonate–based supplements should be taken with food. Dietary intake together with use of calcium supplements should not exceed the UL of 2,500 mg/d for adults.
Iron	Microcytic anemia, pregnancy, medications, and bariatric surgery	Varies: prenatal supplements generally contain about 30 mg of elemental iron; for microcytic iron deficiency: 60 mg of elemental iron taken 3 times/d is recommended	Supplements with iron should be avoided with hemochromatosis.
Magnesium	Constipation, improves glucose control, migraines, refeeding syndrome and malnutrition, alcohol abuse, and malabsorptive disorders	400 mg/d; 600 mg/d for migraines	Serum levels do not correlate with total body stores. High doses can result in diarrhea. Toxicity can develop with impaired renal function or kidney failure.
Zinc	Wound healing, dysgeusia, malabsorptive disorders, vegan diet, and alcohol abuse	<50 mg/d elemental zinc	Supplementation >10 weeks may lead to a copper deficiency and decrease HDL-cholesterol levels. Serum levels are reduced with inflammation and are not an accurate indicator of status. Diuretics increase urinary zinc excretion.
Botanicals
Cinnamon	Lower blood glucose level in type 2 diabetes and prediabetes; has anti-inflammatory benefits	1-2 tsp/d	Ceylon cinnamon recommended over cassia; cassia contains the hepatotoxic ingredient coumarin. Results of clinical studies regarding glucose control are mixed.
Ginger	Reduce pain related to dysmenorrhea and osteoarthritis; may reduce nausea and vomiting during pregnancy	0.5-3 g/d	May interfere with antiplatelet and anticoagulant medications.
Red yeast rice	Reduce serum cholesterol levels	600 mg twice daily	Contains monacolins, which are identical to ingredients in statin drugs such as lovastatin. Moderate drug interactions can occur if taken with other lipid-lowering medications or niacin.
Resveratrol	Prevent cognitive decline, reduce glucose levels and blood pressure, reduce osteoarthritis and rheumatoid arthritis	250-1,000 mg/d	Strong evidence is lacking regarding any established benefits.
Turmeric	NAFLD, inflammation, depression, and severe oral mucositis	1.5 g/d	Bioavailability and absorption enhanced with piperine (an alkaloid in black pepper); has moderate interactions with many medications: antihypertensive, antiplatelet, antidiabetic drugs, in addition to warfarin and tamoxifen.
Other supplements
Protein powders	Increase and meet protein needs	Varies	Whey and plant-based products have been found to be equal in promoting muscle synthesis and increasing muscle mass. Excess protein intake should be avoided with stage 3-4 chronic kidney disease.
Probiotics	Antibiotic-associated diarrhea, bloating, constipation, and IBS	Varies, but products with 1 billion CFU containing species of Lactobacillus and Bifidobacterium typically are recommended	May decreased bloating with use of proton-pump inhibitor Antibiotic-associated diarrhea may be reduced depending on the type of antibiotic and strain of bacteria in product. Adverse effects reported in critically ill patients in ICU.
Apple cider vinegar	Reduce blood glucose levels and weight loss	1 tbsp/d	Fasting postprandial glucose and total cholesterol levels when used for >8 weeks may be reduced; hemoglobin A1c levels may also be reduced. Study results mixed for weight loss. Liquid products recommended vs. pill form.
Omega-3 fatty acids	Reduce risk for heart disease, hypertriglyceridemia, dementia, rheumatoid arthritis, inflammatory bowel disease	1-4 g/d	VITAL trial found taking 460 mg/d of EPA and 380 mg/d DHA did not reduce the risk for cardiovascular disease except in the Black population; risk was reduced with supplementation when intake of fish per week was low.
Abbreviations: CFU, colony-forming unit; d= day; DHA = docosahexaenoic acid; EPA = eicosapentaenoic acid; g = gram; HDL = high-density lipoprotein; IBS = irritable bowel syndrome; ICU = intensive care unit; IU = international units; mcg = microgram; mg = milligram; NAFLD, nonalcoholic fatty liver disease; RDA = Recommended Daily Allowance; tbsp = tablespoon; tsp = teaspoon; UL = Tolerable Upper Intake Level; VITAL = Vitamin D and Omega-3 Trial.

As discussed in chapter 5 on micronutrients, several guidelines are available to help determine if nutrient intake is adequate to avoid developing a deficiency. The Dietary Reference Intake values are reference standards to use for evaluating adequacy of intake and need for dietary supplementation to fill identified gaps.

Efficacy

Supplements can play a role in helping consumers achieve adequacy of intake for various nutrients when intake is insufficient or when food dislikes, allergies, and/or intolerances result in avoidance of particular foods or food groups. For example, adequate vitamin D intake is difficult to achieve because foods other than dairy products tend to have low levels. Supplementation can promote optimal serum levels when dietary intake and sun exposure are missing. Furthermore, individuals with compromised hepatic and renal function are unable to activate vitamin D and so require supplementation. Vitamin D is considered a hormone in addition to being classified as a vitamin, because it is associated with a number of pleiotropic benefits in the body, including promoting healthy skeletal mass, heart health, and overall good health.¹⁵

Other supplements are commonly recommended to avoid deleterious outcomes, such as neural tube defects. Pregnancy and planning for pregnancy often include recommendations for taking supplements with folic acid to avoid neural tube defects developing in babies. Additionally, supplements containing a combination of vitamins C and E, copper, zinc, lutein, and zeaxanthin may slow vision loss in adults with age-related macular degeneration.¹⁶

Individuals with conditions that reduce the availability or absorption of various micronutrients, including use of certain prescription medications (e.g., PPIs), resections of the gastrointestinal tract (e.g., ileal resections, bariatric surgery), or specific issues with organ function (e.g., kidney dialysis) may also benefit from use of certain supplements to avoid developing deficiencies.

Efficacy can be difficult to determine, particularly in available botanical supplements. Difficulty arises when trying to identify plant parts and/or the active component contained in the plant when the active ingredient isn’t known. Quality control and standardization of products are difficult because the makeup of plants varies worldwide. Botanicals can be used as infusions, tinctures or extracts, teas, creams, drinks, tablets, and in powder form. In the United States, there are no requirements or laws that products be standardized, which makes comparing products challenging.

Scientific evidence, the foundation for evidence-based practice, related to dietary supplements is often changing and challenging to discern, for many reasons. It can be difficult to make recommendations because information is often not available, available information is from small studies, evidence is from poorly designed and poorly controlled studies, research is conflicting, the funding source may influence study reporting, and/or standards are lacking to guide dosage and use.

Providing Guidance for Using Dietary Supplements

When providing counseling and suggestions for using dietary supplements, several factors should be considered: Are dietary supplements safe? Which are the best? Are they effective? Is the individual likely to be compliant with taking the supplement?

Counsel individuals that following the guidelines for a healthy lifestyle, including consumption of a well-balanced diet and regular physical activity, is still necessary even when taking supplements. Supplements do not generally provide a variety of phytonutrients or fiber, which are necessary dietary components associated with health and wellness. Additional recommendations when considering the need for supplements are outlined in the “Recommendations to Consider When Recommending Supplements” text box.

When recommending a supplement, it is important to consider if it has been tested via a nonprofit third party with an accredited laboratory. Products with the US Pharmacopeia (USP) or NSF designation have been verified for quality, including that they don’t contain contaminants or toxins, meet the FDA’s GMPs, and can be digested and absorbed in a given time. Health-care professionals should also be aware if any safety recommendations have been issued by agencies, such as the FDA.

Reassessment of need for continued supplementation is warranted to determine if deficiencies have been corrected and to avoid overconsumption. For example, high doses of vitamin D are often prescribed with hypovitaminosis D. However, high-dose supplementation is often only recommended for established safe periods of time. Once levels are repleted, lower doses are generally needed to maintain status. See chapter 5 (Micronutrients) regarding doses to facilitate repletion when deficiencies are diagnosed.

Lastly, the Online Resources text box lists resources, available for health-care providers and consumers, that provide information on various supplements pertaining to clinical evidence, possible side effects, and doses. Resources such as the NATMED PRO database, the German E Commission, and Memorial Sloan Kettering Cancer Center provide essential information for clinicians regarding popular reasons to use various supplements, their clinical relevance, clinical evidence, side effects, and interactions with medications.

Summary

Dietary supplements are used by millions of adults in the United States, and the supplement market is ever growing and generating billions of dollars. Supplements have become a global enterprise, with ingredients and products coming from a variety of countries worldwide. Hence, safety concerns abound, due to lack of oversight and regulation.

Consumers and health-care providers should be knowledgeable and aware of potential benefits and risks associated with use before purchasing and consuming supplements. Dietary approaches should be the foundation for obtaining the necessary nutrients for overall health and wellness, with supplementation supporting dietary intake and considered only when gaps exist for individuals at an increased risk for developing a deficiency or when deficiencies have been diagnosed.

Check your understanding of this chapter with these 2 interactive activities:

References

1. US Food and Drug Administration. Questions and answers on dietary supplements. Updated February 2, 2024. Accessed December 20, 2024. https://www.fda.gov/food/information-consumers-using-dietary-supplements/questions-and-answers-dietary-supplements
2. Zion Market Research. Global dietary supplements market will reach USD 220.3 billion in 2022: Zion Market Research. January 11, 2017. Accessed November 1, 2024. https://globenewswire.com/news-release/2017/01/11/905073/0/en/Global-Dietary-Supplements-Market-will-reach-USD-220-3-Billion-in-2022-Zion-Market-Research.html.
3. Mishra S, Stierman B, Gahche JJ, Potischman N. Dietary supplement use among adults: United States, 2017-2018. NCHS Data Brief. 2021;(399):1–8.
4. US Food and Drug Administration. FDA 101: dietary supplements. Updated June 2, 2022. Accessed July 1, 2023. https://www.fda.gov/consumers/consumer-updates/fda-101-dietary-supplements#:~:text=If%20a%20product%20is%20found,dangerous%20product%20from%20the%20market
5. US Food and Drug Administration. Current Good Manufacturing Practice (CGMP) regulations. Updated May 19, 2023. Accessed July 1, 2023. https://www.fda.gov/drugs/pharmaceutical-quality-resources/current-good-manufacturing-practice-cgmp-regulations
6. Austin SB, Yu K, Liu SH, Dong F, Tefft N. Household expenditures on dietary supplements sold for weight loss, muscle building, and sexual function: disproportionate burden by gender and income. Prev Med Rep. 2017; 6;236–241. doi: 10.1016/j.pmedr.2017.03.016
7. US Food and Drug Administration. Tainted products marketed as dietary supplements. Updated May 18, 2020. Accessed November 2, 2024. https://www.fda.gov/about-fda/fda-pharmacy-student-experiential-program/tainted-products-marketed-dietary-supplements
8. National Institutes of Health Office of Dietary Supplements. Dietary supplements: what you need to know. Updated January 4, 2023. Accessed June 28, 2023. https://ods.od.nih.gov/factsheets/WYNTK-Consumer/
9. Long J. FDA audits climb in FY 2022 for dietary supplement facilities. 2022. Accessed June 30, 2023. https://www.naturalproductsinsider.com/regulatory/fda-audits-climb-fy22-dietary-supplement-facilities
10. US Food and Drug Administration. Health Fraud Product Database. Updated April 14, 2023. Accessed June 30, 2023. https://www.fda.gov/consumers/health-fraud-scams/health-fraud-product-database
11. Asher GN, Corbett AH, Hawke RL. Common herbal dietary supplement-drug interactions. Am Fam Physician. 2017;96(2):101–107.
12. Plastic surgery: medications to avoid before surgery. UCLA Health System. Accessed June 30, 2023. https://www.uclahealth.org/medical-services/surgery/plastic-surgery/patient-resources/medications-avoid-before-surgery
13. US Food and Drug Administration. Information on select dietary supplement ingredients and other substances. Reviewed May 16, 2024. Accessed November 2, 2024. https://www.fda.gov/food/dietary-supplements/information-select-dietary-supplement-ingredients-and-other-substances
14. Johnstone J, Meade M, Lauzier F, et al.; Prevention of Severe Pneumonia and Endotracheal Colonization Trial (PROSPECT) investigators and the Canadian Critical Care Trials group. Effect of probiotics on incident ventilator-associated pneumonia in critically ill patients: a randomized clinical trial. JAMA. 2021;326(11):1024–1033. doi: 10.1001/jama.2021.13355
15. National Institutes of Health Office of Dietary Supplements. Vitamin D. Updated July 26, 2024. Accessed November 2, 2024. https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/
16. Chew EY, Clemons TE, Agron E, et al. Long-term outcomes of adding lutein/zeaxanthin and omega-3 fatty acids to the AREDS supplements on age-related macular degeneration progression: AREDS2 Report. JAMA Ophthalmol. 2022;140(7):692–698. doi: 10.1001/jamaophthalmol.2022.1640
17. Drake VJ. Thiamin. Oregon State University, Linus Pauling Institute, Micronutrient Information Center. Updated July 2021. Accessed May 13, 2023. https://lpi.oregonstate.edu/mic/vitamins/thiamin
18. Drake VJ. Riboflavin. Oregon State University, Linus Pauling Institute, Micronutrient Information Center. Updated August 2021. Accessed May 13, 2023. https://lpi.oregonstate.edu/mic/vitamins/riboflavin
19. Delage B. Niacin. Oregon State University, Linus Pauling Institute, Micronutrient Information Center. Updated December 2017. Accessed June 21, 2023. https://lpi.oregonstate.edu/mic/vitamins/niacin.
20. Drake VJ. Folate. Oregon State University, Linus Pauling Institute, Micronutrient Information Center. Updated October 2023. Accessed November 2, 2024. https://lpi.oregonstate.edu/mic/vitamins/folate
21. Drake VJ. Vitamin B₁₂. Oregon State University, Linus Pauling Institute, Micronutrient Information Center. Updated October 2023. Accessed November 2, 2024. https://lpi.oregonstate.edu/mic/vitamins/vitamin-B12
22. Delage B. Vitamin C. Oregon State University, Linus Pauling Institute, Micronutrient Information Center. Updated July 2018. Accessed November 2, 2024. https://lpi.oregonstate.edu/mic/vitamins/vitamin-C
23. Delage B. Vitamin D. Oregon State University, Linus Pauling Institute, Micronutrient Information Center. Updated July 2017. Accessed November 2, 2024. https://lpi.oregonstate.edu/mic/vitamins/vitamin-D
24. Lonn E, Bosch J, Yusuf S, et al. HOPE and HOPE-TOO Trial Investigators. Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial. JAMA. 2005;293(11):1338–1347. doi:10.1001/jama.293.11.1338
25. Jha P, Flather M, Lonn E, Farkouh M, Yusuf S. The antioxidant vitamins and cardiovascular disease: a critical review of epidemiologic and clinical trial data. Ann Intern Med. 1995;123:860–872. doi:10.7326/0003-4819-123-11-199512010-00009
26. Klein EA, Thompson IM Jr, Tangen CM, et al. Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA. 2011;306(14):1549–1556. doi:10.1001/jama.2011.1437
27. Delage B. Calcium. Oregon State University, Linus Pauling Institute, Micronutrient Information Center. Updated May 2017. Accessed November 2, 2024. https://lpi.oregonstate.edu/mic/minerals/calcium
28. Lopez-Caleya JF, Ortega-Valín L, Fernández-Villa T, Delgado-Rodríguez M, Martín-Sánchez V, Molina AJ. The role of calcium and vitamin D dietary intake on risk of colorectal cancer: systematic review and meta-analysis of case-control studies. Cancer Causes Control. 2022;33(2):167–182. doi:10.1007/s10552-021-01512-3
29. Delage B. Iron. Oregon State University, Linus Pauling Institute, Micronutrient Information Center. Updated April 2016. Accessed November 2, 2024. https://lpi.oregonstate.edu/mic/minerals/iron
30. Volpe SL. Magnesium. Oregon State University, Linus Pauling Institute, Micronutrient Information Center. Updated November 2018. Accessed November 2, 2024. https://lpi.oregonstate.edu/mic/minerals/magnesium
31. Institute of Medicine Panel on Micronutrients. Chapter 12. Zinc. Dietary Reference Intakes for Vitamin A, Vitamin K, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. National Academies Press; 2001:442–501.
32. Deyno, S, Eneyew, K, Seyfe S, et al. Efficacy and safety of cinnamon in type 2 diabetes mellitus and pre-diabetes patients: a meta-analysis and meta-regression. Diabetes Res Clin Pract. 2019;156:107815. doi:10.1016/j.diabres.2019.107815
33. Kizilaslan N, Erdem NZ. The effect of different amounts of cinnamon consumption on blood glucose in healthy adult individuals. Int J Food Sci. 2019;2019:4138534. doi:10.1155/2019/4138534
34. NatMedPro. Ginger. Updated June 29, 2023. Accessed July 10, 2023. https://naturalmedicines-therapeuticresearch-com.ezproxy4.library.arizona.edu/databases/food,-herbs-supplements/professional.aspx?productid=961
35. Tavan A, Noroozi S, Zamiri B, et al. Evaluation the effects of red yeast rice in combination with statin on lipid profile and inflammatory indices; a randomized clinical trial. BMC Nutr. 2022;8(1):138. doi:10.1186/s40795-022-00639-z
36. Zhou DD, Luo M, Huang SY, Effects and mechanisms of resveratrol on aging and age-related diseases. Oxid Med Cell Longev. 2021;2021:9932218. doi:10.1155/2021/9932218
37. Delage B. Curcumin. Oregon State University, Linus Pauling Institute, Micronutrient Information Center. Updated February 2016. Accessed November 2, 2024. https://lpi.oregonstate.edu/mic/dietary-factors/phytochemicals/curcumin
38. Nichele S, Phillips SM, Boaventura BCB. Plant-based food patterns to stimulate muscle protein synthesis and support muscle mass in humans: a narrative review. Appl Physiol Nutr Metab. 2022:47(7):700–710. doi:10.1139/apnm-2021-0806
39. Hill C, Guarner F, Reid G, et al. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014;11:506–514. doi: 10.1038/nrgastro.2014.66
40. Jafarnejad S, Shab-Bidar S, Speakman JR, Parastui K, Daneshi-Maskooni M, Djafarian K. Probiotics reduce the risk of antibiotic-associated diarrhea in adults (18-64 years) but not the elderly (>65 years): a meta-analysis. Nutr Clin Pract. 2016;31:502–513. doi:10.1177/0884533616639399
41. Hadi A, Pourmasoumi M, Najafgholizadeh A, Clark CCT, Esmaillzadeh A. The effect of apple cider vinegar on lipid profiles and glycemic parameters: a systematic review and meta-analysis of randomized clinical trials. BMC Complement Med Ther. 2021;21(1):179. doi:10.1186/s12906-021-03351-w
42. Skulas-Ray AC, Wilson PWF, Harris WS, et al. Omega-3 fatty acids for the management of hypertriglyceridemia: a science advisory from the American Heart Association. Circulation. 2019;140(12) e673–e691. doi:10.1161/CIR.0000000000000709
43. Manson JE, Cook NR, Lee IM, et al. VITAL Research Group. Marine n-3 fatty acids and prevention of cardiovascular disease and cancer. N Engl J Med. 2019;380(1):23–32. doi:10.1056/NEJMoa1811403