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Dietary Supplements for APRNs Part 1: Vitamins Nursing CE Course

1.5 ANCC Contact Hours

1.5 ANCC Pharmacology Hours

About this course:

The purpose of this module is to provide an overview of the various dietary supplements including the potential benefits, risks, and impacts for patients utilizing these products.

Course preview

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The purpose of this module is to provide an overview of the various dietary supplements including the potential benefits, risks, and impacts for patients utilizing these products.

By the completion of this module, the APRN should be able to:

  1. Examine the history of dietary supplements.
  2. Consider the regulatory process of dietary supplements.
  3. Discuss current recommendations for dietary intake of vitamins.
  4. Discuss the difference between fat-soluble and water-soluble vitamins.

Terms

Antioxidants are man-made or natural substances that can prevent or delay various types of cellular damage. They are found in fruits and vegetables or as dietary supplements. Examples are beta-carotene, lutein, lycopene, selenium, and vitamins A, D, and E (US National Library of Medicine [NLM], 2020). 

Dietary supplements are vitamins, minerals, herbs, and other products that can play an important role in health by replacing dietary intake through supplements; they can be in the form of powder, pills, capsules, drinks, or energy bars (NLM, 2018).

Fat-soluble vitamins are similar to oil and do not dissolve in water. They are most abundant in high-fat foods and are better absorbed into circulation when eaten with fat. Fat-soluble vitamins are stored in body tissues and remain there, leading to overdose if a person takes too many over time. The four fat-soluble vitamins in the human diet are vitamins A, D, E, and K (Arnarson, 2017; Youdim, 2019).

Macronutrients are essential nutrients that have a large minimum daily requirement, including proteins, carbohydrates, fats, and water (Youdim, 2019).  

Micronutrients are essential nutrients that are needed in minute amounts, such as vitamins and minerals (Youdim, 2019).

Water-soluble vitamins dissolve in water and are not stored by the body. Most of these vitamins must be replenished via the diet or dietary supplements on a continuous basis since they are not stored. Any excess vitamin in the body is excreted. Vitamin B12 is an exception, as it can be stored in the liver for an extended period of time. Water-soluble vitamins are vitamin C, niacin, pantothenic acid, riboflavin, thiamin, vitamin B6, and vitamin B12 (Youdim, 2019).

History

Our current knowledge of dietary supplements has evolved over the past hundred years significantly; however, since 400 B.C., the link between food and health has been known. See Table 1 for a brief overview of the history of dietary supplements.

Over the past century, there have been 13 essential vitamins identified. These are given the term essential since the body must have them to maintain health and function. In their absence, the human body will not function properly and nutritional diseases will develop. Beyond the 13 essential vitamins, dietary supplements are not well defined. Manufacturers take great liberty in developing a broad range of dietary supplements, and there is little scientific proof of necessity or outcome with their intake. Today, over half of US adults take at least one dietary supplement per day, and there are as many as 80,000 dietary supplement products on the market with an estimated $40 billion in annual sales. With this number of products in use, consistency, quality, and safety are of grave concern to most (Kantor et al., 2016; Mozaffarian et al., 2018).

Regulatory Process

Dietary supplement regulation did not start until early in the 20th century, partly because a structured federal regulatory agency did not exist until 1906. Further, there was little to no knowledge regarding the elements of food responsible for various aspects of health and nutrition until the early 1900s-1920s. In 1994, the US Congress passed the Dietary Supplement Health and Education Act (DSHEA), defining a dietary supplement as a product that supplements the diet under the category of food (rather than a medication). The DSHEA further notes that dietary supplements must contain one or more ingredients (excluding tobacco, but including vitamins, minerals, herbs or other botanicals, amino acids, and other substances) or constituents (component, part, or ingredient of a larger whole, for example, valerenic acid is a constituent of the dietary supplement valerian). According to the DSHEA, supplements are to be taken orally (by mouth) as a capsule, pill, tablet, or liquid and should be labeled on the front panel as a dietary supplement. Products can range from children's vitamins to sports nutrition and weight-loss products for adults. The DSHEA provides the US Food and Drug Administration (FDA) with the regulatory authority and the ability to enforce processes that ensure consumer access to dietary supplements. While the FDA regulates dietary supplements, the process is much less stringent than with other food and drug regulations. Manufacturers do not have to prove that dietary supplements are safe and effective through testing or clinical trials prior to marketing as other drugs require. The DSHEA also mandates that dietary supplements should be produced in compliance with current Good Manufacturing Practices, and the FDA has the authority to remove potentially unsafe products from the market (NIH, 2020b).

When a manufacturer develops a new product, they do not have to notify the FDA unless the product contains a new dietary ingredient (NDI) that includes any vitamin, mineral, or herb that was not on the market prior to October 15, 1994. Of interest, there is no definitive list of dietary ingredients contained in dietary supplements prior to this date, but manufacturers and distributors are expected to determine all ingredients in their supplements and ensure compliance. The FDA notes that a dietary ingredient is "a vitamin; a mineral; an herb or other botanical; an amino acid; a dietary substance for use by man to supplement the diet by increasing total dietary intake; or a concentrate, metabolite, constituent, extract, or combination of any of the above dietary ingredients." In the event of an NDI, the manufacturer is simply required to notify the FDA and provide rationale as to why they feel it is appropriate to add the ingredient, a description of the ingredient, and any identifying published materials that are available (FDA, 2019).

Dietary supplements that are identified with an NDI without notification to the FDA are considered adulterated. Other situations that would classify a dietary supplement as adulterated would include:

  1. If a significant risk of illness or injury with ingestion is present with suggested use;
  2. If there is an imminent hazard to public safety;
  3. If the supplement has been prepared, packed, or stored under conditions that are not consistent with manufacturing regulations; or 
  4. If the label's indication of ordinary use presents the risk of illness (FDA, 2019; NIH, 2020c).

Dietary supplements that have false or misleading labeling are considered misbranded foods. Misbranding provisions are applied if the label does any of the following:

  1. Fails to list each ingredient’s name and quantity;
  2. Fails to identify the product as a dietary supplement; or 
  3. Fails to state from which plant each ingredient is derived (FDA, 2019; NIH, 2020b).

In 2015, the US Department of Health and Human Services (HHS) and the USDA jointly formed the Dietary Guidelines Advisory Committee (DGAC). This committee's foc


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us is to evaluate dietary guidelines and identify common characteristics of healthy diets, identify critical new research, and develop food-based recommendations critical to good health. Of interest, the agencies in tandem with the DGAC published that 50% of adults in the US suffer from preventable, chronic disease, and two-thirds of adults (and nearly one-third of children) in the US are either overweight or obese with poor dietary habits partially responsible for these disparities. The report notes that positive changes to dietary habits have the potential to modify individual patient outcomes related to the impact of preventable disease progression. While this report primarily focuses on good nutrition through a healthy diet, the value and limitations of dietary supplements are also discussed. Dietary supplements are typically utilized for wellness rather than disease treatment; however, there is recognized value in some disease processes. It is advised that healthcare providers discuss the use of dietary supplements with their patients to determine the best supplemental regime for each individual (USDA, 2015).

Dietary supplements may have claims of health, nutrient, structure, or function. Each type of claim has implications based on FDA expectations. Health claims may describe a relationship between a food or dietary supplement ingredient and a reduced risk of disease or health-related condition.  A nutrient content claim describes the amount of a nutrient or dietary substance in a particular product. A structure or function claim describes how the product may affect a body system or organ, i.e., the cardiovascular system or the heart. If a structure or function claim is made, the manufacturer must notify the FDA with the text of the claim at least 30 days before the product is put on the market for sale. There must be a disclaimer added to any structure or function claim that states, "This statement has not been evaluated by the FDA. This product is not intended to diagnose, treat, cure, or prevent any disease" (NIH, 2020c).

Current Recommendations

The Food and Nutrition Board (FNB) is the component of the Institute of Medicine that manages food safety and quality issues; establishes guidelines for adequate dietary intake by individuals; and gives authoritative judgments on the relationship between food intake, nutrition, and overall health. This board is part of the National Academies of Sciences, Engineering, and Medicine (NASEM); part of their task is to provide policy guidance designed to use food and nutrition science to improve the health of Americans. The board was established in 1940, evaluating issues related to the safety and adequacy of the US food supply and continuing with this monitoring today. Part of their study of nutrition is focused on the relationship between food intake, nutrition, health maintenance, and prevention of disease (NASEM, 2018).

The dietary reference intake (DRI) is a general term for a set of reference values the FNB uses to plan and assess nutrient intakes of healthy individuals (USDA, 2015). Also, DRIs can be used to develop optimal diet plans and dietary supplement options. The values often differ based on age and sex, but include:

  • RDA is the average daily level intake that is sufficient to meet the nutritional requirements of most healthy individuals.
  • Adequate intake (AI) is the level assumed to ensure adequate nutrition when evidence is insufficient to determine the RDA. 
  • Tolerable upper intake level (UL) is the maximum daily intake that is unlikely to cause harmful health effects (NIH, n.d.b).

Crucial to remember for healthcare providers and patients is that good nutrition is foundational to good health, and nutritional assessments and education are vital to assisting patients in optimal health and wellness. Dietary supplements are widely marketed to the American consumer and have a variety of ingredients intended to provide multiple benefits for health and wellness (NIH, n.d.b).

Common Categories of Dietary Supplements

For the purposes of this module, dietary supplements discussed are limited to those characterized by the NIH Office of Dietary Health, including a broad overview of vitamins, minerals, herbs/botanicals, amino acid, probiotics, and fish-oil containing products. The NIH Office of Dietary Health offers more in-depth individual educational resources and fact sheets for dietary supplements on their website (NIH, n.d.a).

Vitamins

As previously noted, there are 13 vitamins needed by the body for normal growth, health, and wellness. These vitamins are vitamin A, B vitamins (thiamine, niacin, riboflavin, biotin, pantothenic acid, vitamin B6, vitamin B12, and folate), vitamin C, vitamin D, vitamin E, and vitamin K. Most of these vitamins are obtained from dietary intake. Each vitamin has unique jobs within the body; low levels can lead to health problems and the proper amount can help prevent problems. An example is a lack of vitamin A, which can lead to night blindness. Conversely, high doses of many vitamins can also cause health problems (NLM, 2019).

Vitamin A

Vitamin A is a fat-soluble vitamin that is essential to human health; it aids in normal vision in the dark, promotes normal growth of healthy cells, and keeps the skin healthy. Recommended intakes for vitamin A are referred to as retinol activity equivalents (RAE). 12 Units of beta-carotene or 24 units of other carotenoids make 1 unit of retinol in the body. While Table 3 shows recommended doses for pregnant women, supplemental preformed vitamin A should be avoided during pregnancy (University of Florida, 2016).

Vitamin A is derived from both plant and animal sources. Colorful fruits and vegetables such as sweet potatoes, carrots, cantaloupe, or mangos have the highest amounts of vitamin A and are known as carotenoids. Beta carotene is the most familiar carotenoid and acts as an antioxidant, slowing or preventing cellular damage and decreasing the risk for certain cancers and heart disease. Inadequate intake can cause dry, scaly skin; night blindness; poor growth in children; and increase the risk of infection. Animal sources are known as retinol and include whole milk and liver. Cereals are often fortified with vitamin A. Among individuals that may need extra vitamin A are those with Crohn's disease, cystic fibrosis, liver disease, as well as vegetarians, patients with alcohol use disorder (AUD), and young children (NLM, 2020).

B Vitamins

The B vitamins help the body to make energy from the food ingested and aid in forming red blood cells. B vitamins are water-soluble and found in proteins such as poultry, fish, meat, eggs, and dairy products. Green, leafy vegetables, beans, and peas are loaded with B vitamins as well. Some cereals and bread may be fortified with B vitamins. B vitamin deficiencies can cause diseases such as anemia (B12 or B6 deficiencies). Expanded information of individual B vitamins can be found in Table 2.  

Vitamin C

Vitamin C, also known as ascorbic acid, is a water-soluble vitamin found in foods such as citrus fruits, tomatoes and tomato juice, potatoes, red and green peppers, kiwifruit, broccoli, strawberries, Brussels sprouts, cantaloupe, or fortified cereals or bread. Fresh fruits and vegetables have the highest levels of vitamin C as cooking destroys some of the ascorbic acids. Vitamin C deficiency can lead to scurvy. Initial symptoms include fatigue, malaise, and inflammation of the gums. As the deficiency progresses, petechiae, ecchymosis (bruising), purpura (purple-colored spots on the skin), joint pain, poor wound healing, hyperkeratosis (thickening of the outermost layer of skin), and corkscrew hairs develop. Depression, swollen, bleeding gums, loosening or loss of teeth, and iron deficiency anemia can develop in the later stages. Bone disease can be present in children with vitamin C deficiency. Health risks from excessive vitamin C include diarrhea, nausea, abdominal cramps, or other GI disturbances (NIH, 2020j).

At-risk groups for vitamin C deficiency include:

  • Smokers and passive smokers (second-hand smoke);
  • Infants fed evaporated or boiled milk;
  • Individuals with limited food variety;
  • Those with any type of malabsorption disease such as bariatric surgical patients;
  • End-stage renal disease patients;
  • Hemodialysis patients;
  • Cancer patients (NIH, 2020j)

Vitamin C can be used to prevent certain cancers, including lung, breast, colon, rectum, stomach, oral cavity, larynx, pharynx, and esophagus. High doses of vitamin C can be beneficial to those with terminal cancer but can interact with some chemotherapy. High intake of vitamin C is associated with a reduction in CVD, lower incidence of age-related macular degeneration, and cataracts. It has also been recognized as possible prevention and treatment for the common cold at doses of at least 250 mg/d. However, this has only shown positive results in 50% of extreme exercisers. In the average adult, there was an 8% reduction of cold duration and 14% in children. Vitamin C has shown interactions with chemotherapy and radiation. Cyclophosphamide (Cytoxan), chlorambucil (Leukeran), carmustine (BiCNU), busulfan (Busulfex), thiotepa (Tepadina), and doxorubicin (Adriamycin) effectiveness can be decreased due to the cellular protection of antioxidants, including vitamin C. 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) such as niacin-simvastatin (Zocor) effectiveness can be reduced in the presence of high levels of vitamin C as well (NIH, 2020j). 

Vitamin D

Vitamin D is a fat-soluble vitamin naturally present in only a few foods, including the flesh of fatty fish. Very small amounts of vitamin D are found in beef liver, cheese, and egg yolks. Vitamin D found in these foods is primarily D3. There are a few mushrooms with D2 from their exposure to ultraviolet light under controlled conditions. Other foods that are fortified with vitamin D include the US milk supply, breakfast cereals, and plant-based milk alternatives such as almond, oat, or soy. Most people attain their vitamin D from sun exposure or dietary supplements. Vitamin D2 and D3 are the primary forms in fortified foods and supplements. Vitamin D deficiencies can lead to rickets and osteomalacia (weakened bones). While it is rare to see rickets in the US, it is still reported occasionally, particularly in African American infants and children. Prolonged breastfeeding without vitamin D supplementation can also lead to rickets. Other causes are the use of sunscreen, which deters sun exposure and daycare programs where children have less sun exposure. Groups at risk are breastfed infants, older adults, those with limited sun exposure, dark-skinned people, those with fat malabsorption (IBD, cystic fibrosis, celiac disease, or liver disease), obese patients, or those who have a history of bariatric surgery (NIH, 2020k).

Vitamin D is used therapeutically for those at risk or who have osteoporosis, colorectal cancer, type 2 diabetes, hypertension, glucose intolerance, and multiple sclerosis (MS). There is some evidence that vitamin D can be used to prevent myocardial infarction (MI), stroke, and other CVD, but the evidence is not significant for improvement or decreased risk. Drug interactions with vitamin D include glucocorticoids such as prednisone (Deltasone), the weight-loss drug orlistat (Alli), and the cholesterol-lowering drug cholestyramine (Questran), all of which can interfere with the absorption of vitamin D. Phenobarbital (Luminol) and phenytoin (Dilantin) increase the metabolism of vitamin D and reduce calcium absorption (NIH, 2020k).

Serum levels of vitamin D and health implications are included in Table 4 below. 

Vitamin D toxicity can cause adverse effects, including anorexia, weight loss, polyuria, or heart arrhythmias. Blood calcium levels can increase, causing vascular and tissue calcification with damage to the heart, kidneys, and blood vessels. The risk for kidney stones increases by 17% in postmenopausal women who are taking 1,000 mg/d of calcium along with 400 IU vitamin D daily or higher doses (NIH, 2020k).

Vitamin E

Naturally occurring vitamin E is found in eight chemical forms (alpha-, beta-, gamma-, and delta-tocopherol; alpha-, beta-, gamma-, and delta-tocotrienol) and is fat-soluble. Only alpha-tocopherol is recognized to meet human requirements. Vitamin E is primarily sold in IUs. One mg of alpha-tocopherol is equivalent to 1.49 IU of the natural form, or 2.22 IU of the synthetic form of vitamin E. Sources of vitamin E include nuts, seeds, vegetable oils, green leafy vegetables, and fortified cereals. Specific foods high in vitamin E (alpha-tocopherol) are wheat germ oil, sunflower seeds, almonds, sunflower oil, safflower oil, hazelnuts, peanut butter, corn oil, spinach, and broccoli. Dietary supplements typically provide only alpha-tocopherol and contain 100 IU of natural vitamin E in each capsule (NIH, 2020l).

Vitamin E deficiency is rare. However, premature babies with a birth weight below 1500 grams can be vitamin E deficient. Supplementation can reduce the risk of complications, including infections or retinal issues. Those with fat malabsorption disorders are more likely to become deficient. Symptoms include peripheral neuropathy, ataxia, skeletal myopathy, retinopathy, and impaired immune response. The risk of heart disease, cancer (colon, bladder, and breast), eye disorders (age-related macular degeneration or cataracts), and cognitive decline may be decreased with vitamin E supplementation. However, the daily use of large doses of vitamin E supplements has been associated with an increased risk of prostate cancer. Medication interactions include anticoagulant or antiplatelet medications such as warfarin (Coumadin), cholesterol-lowering drugs such as simvastatin (Zocor) and niacin. Other interactions include most chemotherapy agents and radiation therapy (NIH, 2020l).

Vitamin K

Vitamin K is a naturally occurring fat-soluble vitamin. The primary form is phylloquinone (vitamin K1) and is found in green, leafy vegetables. Menaquinones (vitamin K2) are primarily of bacterial origin and are produced by bacteria in the human gut. Vitamin K assists with blood clotting. Food sources include spinach, broccoli, iceberg lettuce, kale, turnip greens, collard greens and other green leafy vegetables, edamame, pumpkin, pomegranate juice, soybean oil, vegetable oils, and some fruits. Vitamin K deficiencies can lead to bleeding and hemorrhage, reduced bone mineralization, and osteoporosis. Groups at risk include newborns not treated with vitamin K at birth, individuals with malabsorption disorders such as cystic fibrosis, celiac disease, IBD, short bowel syndrome, and those with a history of bariatric surgery (NIH, 2020m). 

Therapeutic indications for vitamin K include osteoporosis and coronary heart disease. However, the data is mixed on the therapeutic outcomes according to the NIH (2020m). A clinical trial demonstrated that vitamin K supplementation at 180 mcg/d for three years decreased the loss of height in the lower thoracic region of the vertebrae in postmenopausal women. However, another study combined 630 mg of calcium, 400 IU vitamin D3, and 180 mcg/d of vitamin K for 12 months with no effect on bone mineral density in elderly men or women. While studies have been positive in the Netherlands with postmenopausal women and another on both healthy men and women in the US, there is no clear data that vitamin K reduces the risk of arterial calcification or lowers the risk of coronary disease. There are medication interactions with vitamin K, including warfarin (Coumadin) and similar anticoagulants. Since vitamin K assists with clotting, these drugs work against each other (antagonists). Vitamin K can increase or decrease the therapeutic effect of anticoagulants. Dietary consumption of vitamin K, such as green, leafy vegetables, should be eaten consistently to avoid variations in clotting times. Antibiotics, particularly cephalosporins such as cefoperazone (Cefobid), can diminish vitamin K levels as they may destroy the vitamin K producing bacteria in the gut. Bile acid sequestrants such as cholestyramine (Questran) and colestipol (Colestid) decrease cholesterol levels by preventing the reabsorption of bile acids. They also decrease the absorption of vitamin K and other fat-soluble vitamins. Orlistat (Alli) decreases the absorption of fat-soluble vitamins, including vitamin K. No adverse effects are noted with higher levels of vitamin K ingestion, and there is a low potential for toxicity (NIH, 2020m).

Factsheet for Vitamins

Dietary Supplement and Potential Benefits

Implications/Alerts

Vitamin A is needed for immune function, fetal development, vision, and supporting cell growth.

Signs and symptoms of vitamin A deficiency may include:

  • Dry, scaly skin
  • Night blindness
  • Poor growth in children
  • Increased risk of infection

At risk groups for deficiencies:

  • Crohn's disease
  • Cystic fibrosis
  • Liver disease
  • Vegetarians
  • Patients with alcohol use disorder (AUD)
  • Young children

Vitamin B1 (thiamine) prevents complications of the nervous system, brain, muscles, heart, stomach, and intestines and is also involved in the flow of electrolytes into and out of muscle and nerve cells.

Early signs of thiamine deficiency may include loss of appetite, fatigue, irritability, reduced or absent reflexes, tingling sensation in the extremities, muscle weakness, blurry vision, nausea or vomiting, arrhythmias, shortness of breath, or delirium (particularly in elderly patients)

Deficiency can lead to:

  • Beriberi
  • Wernicke-Korsakoff syndrome (primarily in the presence of AUD)

Vitamin B1 (thiamine) dietary supplementation can interact with:

  • Chemotherapy with 5-fluorouracil (Adrucil)
  • Furosemide (Lasix)
  • Phenytoin (Dilantin)

At risk groups for deficiencies:

  • Patients with AUD
  • Older adults
  • HIV/AIDS patients
  • Diabetics
  • Bariatric surgery history

Vitamin B2 (riboflavin) is needed for growth and overall good health and helps the body break down carbohydrates, proteins and fats to produce energy, and it allows oxygen to be used by the body

Signs and symptoms of riboflavin deficiency may include:

  • Endocrine abnormalities such as thyroid deficiency
  • Skin disorders
  • Hyperemia (excess blood)
  • Edema of mouth and throat
  • Angular stomatitis (lesions at corners of the mouth)
  • Cheilosis (swollen, cracked lips)
  • Hair loss
  • Reproductive problems
  • Sore throat
  • Itchy eyes
  • Anemia and cataracts with prolonged deficiency
  • Migraine headaches
  • Increased colorectal cancer risk

At risk groups for deficiency

  • Vegetarian athletes
  • Pregnant or lactating women and their infants
  • Vegans with little or no milk consumption
  • Infantile Brown-Vialetto-Van Laere syndrome patients

Vitamin B3 (niacin) has a wide range of uses in the body, helping functions in the digestive system, skin and nervous system.

Deficiencies of vitamin B3 (niacin) may present with:

  • Pellagra (pigmented rash or brown discoloration of skin exposed to sunlight)
  • Irritated or red skin
  • Headaches
  • Fatigue
  • Anxiety or depression
  • Inability to concentrate
  • Dizziness
  • Poor circulation
  • Increased risk of cancer in women

Drug interactions include:

  • Rifampin, isoniazid, and pyrazinamide (Rifater)
  • Antidiabetic medications

At risk populations for deficiency include:

  • Anorexia
  • HIV/AIDS patients
  • Patients with AUD
  • Inflammatory bowel disease (IBD) patients
  • Liver cirrhosis patients
  • Hartnup disease patients
  • Carcinoid syndrome patients

Vitamin B5 (pantothenic acid) is necessary blood cells production, and aids in converting food into energy.

Deficiencies of vitamin B5 (pantothenic acid) may present with: 

  • Numbness and burning of the hands and feet
  • Headache
  • Fatigue
  • Irritability
  • Restlessness
  • Disturbed sleep
  • Gastrointestinal (GI) disturbances with anorexia
  • Hyperlipidemia

At risk populations for deficiency:

  • Individuals with pantothenate kinase-associated neurodegeneration-2 mutation (PKAN)

Vitamin B6 (pyridoxine) affects mood, appetite, sleep, and thinking by turning food into energy and helping the blood carry oxygen to the entire body.

Signs and symptoms of vitamin B6 (pyridoxine) deficiency may include:

  • Microcytic anemia
  • Electroencephalographic (EEG) abnormalities
  • Dermatitis with cheilosis 
  • Glossitis (swollen tongue)
  • Depression/confusion
  • Weakened immune function
  • Irritability, abnormally acute hearing, and convulsive seizures in infants

Medication interactions include:

  • Cycloserine (Seromycin)
  • Valproic acid (Depakene)
  • Carbamazepine (Tegretol)
  • Phenytoin (Dilantin)
  • Levetiracetam (Keppra)
  • Theophylline (Theolair)

At risk populations for deficiency:

  • Patients with impaired renal function 
  • Patients with autoimmune disorders such as rheumatoid arthritis (RA)
  • Patients with AUD

Vitamin B7 (biotin) promotes nervous system functioning and helps the body metabolize fats, carbohydrates, and protein.

Signs and symptoms of vitamin B7 (biotin) deficiency may include:

  • Thinning hair
  • Scaly, red rash around body openings (eyes, nose, mouth, perineum)
  • Conjunctivitis 
  • Lactic acidosis
  • Aciduria 
  • Seizures
  • Skin infection
  • Brittle nails
  • Depression
  • Lethargy
  • Hallucinations
  • Paresthesia of the extremities
  • Hypotonia and developmental delays in infants
  • Rash and unusual distribution of facial fat

Medication interactions include:

  • Carbamazepine (Tegretol)
  • Primidone (Mysoline)
  • Phenytoin (Dilantin)
  • Phenobarbital (Luminal)
  • Also interacts with laboratory tests for thyroid function

At risk populations for deficiency:

  • Biotinidase deficiency (rare autosomal recessive disorder) patients
  • Patients with AUD
  • Pregnant and breastfeeding women

Vitamin B9 (folic acid) is needed to produce red blood cells and for the synthesis of DNAA and helps with tissue growth and cell function.

Signs and symptoms of a folic acid deficiency may include:

  • Megaloblastic anemia 
    • Weakness
    • Fatigue
    • Difficulty concentrating
    • Irritability
    • Headache
    • Heart palpitations
    • Shortness of breath
  • Soreness in and shallow ulcerations on the tongue and oral mucosa
  • Skin, hair, nail changes
  • GI symptoms
  • Elevated blood concentrations of homocysteine
  • Women with folate deficiencies are at risk of having infants with low birth weight, neural tube defects, preterm delivery, or fetal growth retardation
  • Several diseases in which folate deficiency may play a role include: 
    • Autism spectrum disorder
    • Cancer
    • CVD and stroke
    • Dementia, cognitive function, and Alzheimer’s disease (AD)
    • Depression
    • Congenital heart defects, and other congenital abnormalities

Medication interactions include:

  • Methotrexate (Trexall)
  • Phenytoin (Dilantin)
  • Carbamazepine (Tegretol)
  • Valproic acid (Depakene)
  • Sulfasalazine (Azulfidine)

At risk populations for deficiency:

  • Patients with AUD
  • Women of childbearing age
  • Pregnant women
  • Patients with a malabsorptive disorder
  • People with methylenetetrahydrofolate reductase (MTHFR) polymorphism

Vitamin B12 (cyanocobalamin) is involved in red blood cell production, brain health, and DNA synthesis but cyanocobalamin is the synthetic form of vitamin B12 that is most frequently used in supplements.

Signs and symptoms of vitamin B12 (cyanocobalamin) deficiency may include: 

  • Megaloblastic anemia
  • Fatigue
  • Weakness
  • Constipation
  • Loss of appetite
  • Weight loss
  • Numbness and tingling of hands and feet
  • Difficulty with balance
  • Depression
  • Confusion
  • Dementia
  • Poor memory
  • Soreness of tongue or mouth
  • Infant symptoms include failure to thrive, movement disorders, developmental delays, megaloblastic anemia

Medication interactions include:

  • Chloramphenicol (Chloromycetin)
  • Omeprazole (Prilosec)
  • Lansoprazole (Prevacid)
  • Cimetidine (Tagamet)
  • Famotidine (Pepcid)
  • Ranitidine (Zantac)
  • Metformin (Glucophage)

At risk populations for deficiency:

  • Older adults
  • Pernicious anemia patients
  • Those with GI disorders
  • Bariatric surgery history
  • Vegetarians
  • Pregnant and lactating women and their infants

Vitamin C is an antioxidant that helps to strengthen the immune system and protect cells from destruction or damage that is linked to many diseases.

Signs and symptoms of vitamin C deficiency may include:

  • Fatigue
  • Malaise
  • Inflammation of the gums
  • Petechiae, 
  • Ecchymosis (bruising)
  • Purpura (purple-colored spots on the skin)
  • Joint pain
  • Poor wound healing
  • Hyperkeratosis (thickening of the outermost layer of the skin)
  • Corkscrew hairs
  • Depression
  • Swollen, bleeding gums
  • Loosening of teeth
  • Iron deficiency anemia

Medication/treatment interactions include:

  • Chemotherapy such as cyclophosphamide (Cytoxan), chlorambucil (Leukeran), carmustine (BiCNU), busulfan (Busulfex), thiotepa (Thioplex), and doxorubicin (Adriamycin) 
  • Radiation
  • 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) such as niacin-simvastatin (Zocor) 

At risk groups for vitamin C deficiency include:

  • Smokers and passive smokers (second-hand smoke)
  • Infants fed evaporated or boiled milk
  • Individuals with limited food variety
  • Those with any type of malabsorption disease such as bariatric surgical patients
  • End-stage renal disease patients
  • Hemodialysis patients
  • Cancer patients

Vitamin D has several functions including regulation of the absorption of calcium and phosphorus as well as facilitating normal immune system function.

Signs and symptoms of vitamin D deficiency may include:

  • Osteomalacia (weakened bones)
  • Rickets
  • Increased risk of colon cancer
  • Increased risk of heart disease
  • Increased risk of MS

Medication interactions include:

  • Glucocorticoids such as prednisone (Deltasone)
  • The weight-loss drug orlistat (Alli)
  • The cholesterol-lowering drug cholestyramine (Questran)
  • Phenobarbital (Luminol) and phenytoin (Dilantin) increase the metabolism of vitamin D and reduce calcium absorption

At risk groups for vitamin D deficiency include:

  • Breastfed infants
  • Older adults
  • Those with limited sun exposure
  • Dark-skinned people
  • Those with fat malabsorption (IBD, cystic fibrosis, celiac disease, or liver disease), obese patients, or those who have a history of bariatric surgery

Vitamin E is an antioxidant and helps protect cells from damage.

Signs and symptoms of vitamin E deficiency may include:

  • Peripheral neuropathy
  • Ataxia
  • Skeletal myopathy
  • Retinopathy
  • Impaired immune response
  • Increase risk of heart disease
  • Increased risk of colon, bladder, or breast cancer
  • Increased risk of age-related macular degeneration or cataracts
  • Cognitive decline

Medication interactions include:

  • Anticoagulants such as warfarin (Coumadin)
  • Cholesterol-lowering drugs such as simvastatin (Zocor)
  • Niacin

At risk groups for Vitamin E deficiency include:

  • Premature babies below 1500 grams
  • Those with fat malabsorption (IBD, cystic fibrosis, celiac disease, or liver disease), obese patients, or those who have a history of bariatric surgery

Vitamin K plays a role in blood clotting, bone metabolism, and regulation of blood calcium levels and is needed to produce prothrombin, a clotting factor.

Signs and symptoms of vitamin K deficiency may include:

  • Bleeding or hemorrhage
  • Reduced bone mineralization and osteoporosis

Medication interactions include:

  • Anticoagulants such as warfarin (Coumadin)
  • Cephalosporins such as cefoperazone (Cefobid)
  • Bile acid sequestrants such as cholestyramine (Questran) and colestipol (Colestid)
  • Orlistat (Alli) decreases the absorption of fat-soluble vitamins

At risk groups for Vitamin K deficiency include:

  • Newborns not treated with vitamin K at birth
  • Those with fat malabsorption (IBD, cystic fibrosis, celiac disease, or liver disease), obese patients, or those who have a history of bariatric surgery 

                                                                                                                 (Healthline, 2018; NIH, n.d.c., 2020a, 2020d, 2020e, 2020f, 2020g, 2020h, 2020i, 2020j, 2020k, 2020l, 2020m; Sullivan, 2017)


RDAs of Vitamins

Vitamin

Males aged 14+

Females aged 14+

Pregnancy

Breastfeeding

Vitamin A (measured in RAEs)

900 mcg RAE/d

700 mcg RAE/d

750-770 mcg RAE/d

1200-1300 mcg RAE/d

Vitamin B1 (thiamine)

1.2 mg/d

1.0-1.1 mg/d

1.4 mg/d

1.4 mg/d

Vitamin B2 (riboflavin)

1.3 mg/d

1.0-1.1 mg/d

1.4 mg/d

1.6 mg/d

Vitamin B3 (niacin, measured in niacin equivalency [NE])

16 NE/d

14 NE/d

18 NE/d

17 NE/d

Vitamin B5 (pantothenic acid)

5 mg/d

5 mg/d

6 mg/d

7 mg/d

Vitamin B6

1.3 mg/d

1.2-1.3 mg/d

1.9 mg/d

2 mg/d

Vitamin B7 (biotin)

25-30 mcg/d

25-30 mcg/d

30 mcg/d

35 mcg/d

Vitamin B9 (folic acid, measured in dietary folate equivalents [DFE])

400 mcg DFE/d

400 mcg DFE/d

600 mcg DFE/d

500 mcg DFE/d

Vitamin B12

2.4 mcg/d

2.4 mcg/d

2.6 mcg/d

2.8 mcg/d

Vitamin C

75-90 mg/d

65-75 mg/d

80-85 mg/d

115-120 mg/d

Vitamin D (measured in international units [IU])

600 IU 

600 IU 

600 IU 

600 IU 

Vitamin E

15 mg/d

15 mg/d

15 mg/d

19 mg/d

Vitamin K

75-120 mcg/d

75-90 mcg/d

75-90 mcg/d

75-90 mcg/d

                                                                                                                           (Healthline, 2018; NIH, 2020a, 2020d, 2020e, 2020f, 2020g, 2020h, 2020i, 2020j, 2020k, 2020l, 2020m; Sullivan, 2017)


References

Arnarson, A. (2017). The fat-soluble vitamins: A, D, E, and K. Healthline. https://www.healthline.com/nutrition/fat-soluble-vitamins

Healthline. (2018). 11 signs and symptoms of thiamine (vitamin B1) deficiency. https://www.healthline.com/nutrition/thiamine-deficiency-symptoms

Kantor, E. D., Rehm, C. D., Du, M., White, E., & Givannucci, E. L. (2016). Trends in dietary supplement use among US adults from 1999-2012. JAMA, 316(14) 1464-1474. https://doi.org/ 10.1001/jama.2016.14403.

Mozaffarian, D., Rosenberg, I., & Uauy, R. (2018). History of modern nutrition science-implications for current research, dietary guidelines, and food policy. BMJ, 361, k2392. https://doi.org/10.1136/bmj.k2392.

The National Academies of Sciences, Engineering and Medicine. (2018). Food and nutrition board. http://nationalacademies.org/hmd/about-hmd/leadership-staff/hmd-staff-leadership-boards/food-and-nutrition-board.aspx

The National Institutes of Health. (n.d.a). Dietary supplement fact sheets. https://ods.od.nih.gov/factsheets/list-all/

The National Institutes of Health. (n.d.b). Nutrient recommendations: Dietary reference intakes (DRI). https://ods.od.nih.gov/Health_Information/Dietary_Reference_Intakes.aspx

The National Institutes of Health. (n.d.c). Promoting vitamin C. https://profiles.nlm.nih.gov/spotlight/mm/feature/medicine

The National Institutes of Health. (2020a). Biotin. https://ods.od.nih.gov/factsheets/Biotin-HealthProfessional/

The National Institutes of Health. (2020b). Dietary and herbal supplements. https://www.nccih.nih.gov/health/dietary-and-herbal-supplements

The National Institutes of Health. (2020c). Dietary supplements. https://ods.od.nih.gov/factsheets/DietarySupplements-HealthProfessional/#h1

The National Institutes of Health. (2020d). Folate. https://ods.od.nih.gov/factsheets/Folate-HealthProfessional/

The National Institutes of Health. (2020e). Pantothenic acid. https://ods.od.nih.gov/factsheets/PantothenicAcid-HealthProfessional/

The National Institutes of Health. (2020f). Riboflavin. https://ods.od.nih.gov/factsheets/Riboflavin-HealthProfessional/

The National Institutes of Health. (2020g) Vitamin A. https://ods.od.nih.gov/factsheets/VitaminA-HealthProfessional/

The National Institutes of Health. (2020h). Vitamin B6. https://ods.od.nih.gov/factsheets/VitaminB6-HealthProfessional/

The National Institutes of Health. (2020i). Vitamin B12. https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/

The National Institutes of Health. (2020j). Vitamin C. https://ods.od.nih.gov/factsheets/VitaminC-HealthProfessional/

The National Institutes of Health. (2020k). Vitamin D. https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/

The National Institutes of Health. (2020l). Vitamin E. https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/

The National Institutes of Health. (2020m). Vitamin K. https://ods.od.nih.gov/factsheets/vitaminK-HealthProfessional/

Smith, R. (2004). Let food be thy medicine…. BMJ, 328(7433). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC318470/

Sullivan, D. (2017). What’s to know about vitamin B3 deficiency? https://www.medicalnewstoday.com/articles/319429

Swan, J.P. (2015). The history of efforts to regulate dietary supplements in the USA. Drug Testing and Analysis, 8(3-4), 271-282. https://doi.org/10.1002/dta.1919.

University of Florida. (2016). Facts about vitamin A. https://edis.ifas.ufl.edu/pdffiles/fy/fy20600.pdf

US Department of Agriculture. (2015). Scientific report of the 2015 dietary guidelines advisory committee. https://health.gov/sites/default/files/2019-09/Scientific-Report-of-the-2015-Dietary-Guidelines-Advisory-Committee.pdf

US Food & Drug Administration. (2019). New dietary ingredients in dietary supplements: Background for industry. https://www.fda.gov/food/new-dietary-ingredients-ndi-notification-process/new-dietary-ingredients-dietary-supplements-background-industry#what_is

US National Library of Medicine. (2018). Dietary supplements. https://medlineplus.gov/dietarysupplements.html

US National Library of Medicine. (2019). Vitamins. https://medlineplus.gov/vitamins.html

US National Library of Medicine. (2020). Vitamin A. https://medlineplus.gov/vitamina.html

Venkatraman, S. & Dandekar, S. (2015). Nutrition and biochemistry for nurses (2nd ed.). Elsevier.

Youdim, A. (2019). Overview of nutrition. Merck Manual. https://www.merckmanuals.com/professional/nutritional-disorders/nutrition-general-considerations/overview-of-nutrition?qt=&sc=&alt=

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