11

Food and Nutrient Delivery: Bioactive

Substances and Integrative Care
Kelly Morrow, MS, RDN, FAND

KEY TERMS
adverse events (AEs) complementary and integrative medicine megadose
acupuncture (CIM) meridians
alternative medicine dietary supplement moxibustion
American Botanical Council Dietary Supplement Health and naturopathy
American Herbalists Guild Education Act of 1994 (DSHEA) National Center for Complementary
Ayurveda Dietary Supplement Label Database and Integrative Health (NCCIH)
bioactive compound drug nutrient interaction (DNI) new dietary ingredient (NDI)
botanical medicine East Asian medicine pharmacognosy
chi (qi) excipients phytochemical
chiropractic medicine functional medicine phytotherapy
Codex Alimentarius Commission (Codex) generally recognized as safe (GRAS) structure function claim
Commission E Monographs health claim subluxation
complementary medicine holistic medicine third party certification
complementary and alternative medicine homeopathy Tolerable Upper Limit (UL)
(CAM) integrative medicine vis medicatrix naturae

Functional medicine is another iteration of holistic medicine that

COMPLEMENTARY AND INTEGRATIVE MEDICINE has gained esteem in recent years. It shifts the disease-centered focus of
Some people may be confused by the multiple names used to describe conventional medical practice to a more individualized and patient-
natural medicine approaches. Holistic medicine, from the Greek word centered approach (IFM, 2018). The goal is to evaluate the whole person
holos, means “whole.” Holistic therapies are based on the theory that rather than individual symptoms or organs and to consider care in rela-
health is a vital dynamic state that is determined by the balance between tion to both prevention and treatment of chronic disease. Functional
physical, mental, and spiritual parameters. Vis medicatrix naturae, the medicine practitioners, including medical doctors, naturopathic doc-
healing force of nature, is the underlying precept of holistic medicine. tors, chiropractors, nurse practioners, and dietitians, acknowledge a
The philosophy states that when a person lives according to the laws of web-like interconnectedness of internal physiologic factors within the
nature, the body has the ability to self-heal or the overall health of the body. Acting within their scope of practice, they use nutrition therapy,
individual will improve. Examples would include the adoption of a dietary supplements, lifestyle modifications, and physical manipulations
whole foods, mostly unrefined diet, maintaining a level of physical ac- as the foundation of medical care. Functional medicine providers assess
tivity, use of plant-based (herbal) medicines and dietary supplements, for core imbalances, including dietary intake, hormones and neu-
and meditation to reduce stress. This theory is primarily applied to con- rotransmitters, markers of oxidative stress, environmental exposures,
ditions where diet and lifestyle influence health to a large degree such as immune function, and psychological and spiritual health.
cardiovascular disease, diabetes, and many inflammatory conditions. The Academy of Nutrition and Dietetics (AND) practice group,
Alternative medicine refers to nonmainstream therapies used in place of Dietitians in Integrative and Functional Medicine (DIFM), has devel-
conventional medicine. For example, the use of an herbal preparation oped a nutrition-oriented functional medicine radial for dietetics
instead of a drug. Integrative medicine and complementary medicine practitioners to assess clients using Integrative and Functional Medical
refer to holistic therapies used in combination with conventional medi- Nutrition Therapy (IFMNT) (Noland, 2019). A functional nutrition
cine. Most people who use holistic or nonmainstream therapies also use assessment can overlap with the nutrition care process (NCP) and in-
conventional medicine (National Center for Complementary and Inte- cludes expanded categories in the clinical, biochemical, and physical
grative Health [NCCIH], 2018; see Tables 11.1 and 11.2). domains (see Chapter 5 and Fig. 5.9).

USE OF COMPLEMENTARY AND INTEGRATIVE

THERAPIES
Portions of this chapter were written by Cynthia A. Thomson, PhD, According to the National Center for Complementary and Integrative
RDN, for the previous edition of this text. Health (NCCIH), almost 53% of adults and 12% of children in the

187
188 PART II Nutrition Diagnosis and Intervention

TABLE 11.1 Common Holistic Therapies According to the National Center for Complementary
and Integrative Health (NCCIH)
Complementary and Integrative Medical systems Naturopathy, traditional Chinese medicine (also known as East Asian medicine),
Ayurveda, and homeopathy
Mind/Body therapies Meditation, prayer, art or music therapy, and cognitive behavior therapy
Biologically based therapies Herbs, whole-foods diets, and nutrient supplementation
Manipulative therapies Massage, chiropractic medicine, osteopathy, and yoga
Energy therapies Qi gong, magnetic therapy, or reiki
National Center for Complementary and Integrative Health (NCCIH). Complementary, Alternative or Integrative Health: What’s In a Name? http://
[Link]/health/whatiscam.

TABLE 11.2 Description of Commonly Used Complementary and Integrative Therapies

Naturopathy Naturopathy is a form of primary care medicine that uses the healing power of nature, vis medicatrix naturae, to restore and maintain
(Naturopathic optimum health.
Medicine) Guiding principles include the following:
Primum non nocere—First do no harm
Tolle causam—Treat the root cause of illness
Docere—Doctor as teacher
Therapeutic methods and substances are used that work in harmony with a person’s self-healing process, including diet and nutrient
therapy, botanical medicine, psychotherapy, physical and manipulative therapy, minor surgery, prescription medicines, naturopathic
obstetrics (natural childbirth), homeopathy, and acupuncture.
Licensed in the United States to practice in 23 states and 2 territories.
Training includes pathology, microbiology, histology, physical and clinical diagnosis, pharmacognosy (clinical training in botanical
medicine), hydrotherapy, physiotherapy, therapeutic nutrition, and homeopathy.
Chiropractic Chiropractic therapy embraces many of the same principles as naturopathy, particularly the belief that the body has the ability to heal
itself and that the practitioner’s role is to assist in that process. Like naturopathy, chiropractic care focuses on wellness and
prevention and favors noninvasive treatments.
Chiropractors do not prescribe drugs or perform surgery.
The focus is on locating and removing interferences to the body’s natural ability to maintain health, called subluxations (specifically
musculoskeletal problems that lead to interference with the proper function of the nervous and musculoskeletal systems).
Therapeutic approach is the manual manipulation of the body, such as spinal adjustment and massage and lifestyle recommendations,
including physical exercises and stretching.
Two fundamental precepts: (1) The structure and condition of the body influence how well the body functions, and (2) the mind-body
relationship is important in maintaining health and in promoting healing.
Licensed and regulated in all 50 states and in 30 countries.
Must complete a 4-year program from a federally accredited college of chiropractic and, like other licensed practitioners, successfully
pass an examination administered by a national certifying body.
Homeopathy The root words of homeopathy are derived from the Greek homios, meaning like and pathos, meaning suffering. Homeopathy is a medical
theory and practice advanced to counter the conventional medical practices of 200 years ago. It endeavors to help the body heal itself by
treating like with like, commonly known as the “law of similars.” The law of similars is based on the theory that, if a large amount of a
substance causes symptoms in a healthy person, a smaller amount of the same substance can be used to treat an ill person.
Samuel Hahnemann, an eighteenth-century German physician, is credited with founding homeopathy.
The amounts of the remedies used in homeopathic medicines are extremely diluted. According to homeopathic principles, remedies are
potentized and become more powerful through a shaking process called succussion.
Homeopathic tinctures are made from a variety of source materials including botanicals, minerals, and animal tissues. Dosages are
based on the following dilutions. A remedy becomes stronger the more it is diluted.
X: 1 drop tincture in 10 drops water
C: 1 drop tincture in 100 drops water
M: 1 drop tincture in 1000 drops water
The minimum-dose principle means that many homeopathic remedies are so dilute that no actual molecules of the healing substance
can be detected by chemical tests.
The goal of homeopathy is to select a remedy that will bring about a sense of well-being on all levels—physical, mental, and
emotional—and that will alleviate physical symptoms and restore the patient to a state of wellness and creative energy.
Although this form of medicine has a long history of use, clinical evidence on the efficacy of homeopathy is highly contradictory. In 2017,
the FDA proposed new safety regulations for homeopathic medicines, specifically for those that contain potentially toxic substances or
are used for life threatening conditions. This is especially significant for those who are vulnerable (infants and children, the elderly, and
immune compromised). Homeopathic treatments are highly individualized using thousands of remedy combinations which makes the
practice difficult to study using randomized and blinded trials. This presents a research challenge that will not soon be overcome.
 CHAPTER 11 Food and Nutrient Delivery: Bioactive Substances and Integrative Care 189

TABLE 11.2 Description of Commonly Used Complementary and Integrative Therapies—cont'd

East Asian medicine Based on the concept that energy, also termed chi (qi) or life-force energy, is central to the functioning of the body. Chi is the intangible force
that animates life and enlivens all activity. Wellness is a function of the balanced and harmonious flow of chi, whereas illness or disease
results from disturbances in its flow. Wellness also requires preserving equilibrium between the contrasting states of yin and yang (the dual
nature of all things). The underlying principle is preventive in nature, and the body is viewed as a reflection of the natural world.
Four substances—blood, jing (essence, substance of all life), shen (spirit), and fluids (body fluids other than blood)—constitute the
fundamentals.
The nutritional modality has several components: food as a means of obtaining nutrition, food as a tonic or medicine, and the absten-
tion from food (fasting). Foods are classified according to taste (sour, bitter, sweet, spicy, and salty) and property (cool, cold, warm,
hot, and plain) to regulate yin, yang, chi, and blood.
The meridians are channels that carry chi and blood throughout the body. These are not channels per se, but rather they are invisible
networks that act as energy circuits, unifying all parts of the body and connecting the inner and the outer body; organs are not
viewed as anatomic concepts but as energetic fields.
Acupuncture Acupuncture is the use of thin needles, inserted into points on the meridians, to stimulate the body’s chi, or vital energy. Moxibustion,
the application of heat using moxa, dried leaves from mugwort, along meridian acupuncture points for the purpose of affecting chi and
blood so as to balance substances and organs, is related to acupuncture. This therapy is used to treat disharmony in the body, which
leads to disease. Disharmony, or loss of balance, is caused by a weakening of the yin force in the body, which preserves and nurtures
life, or a weakening of the yang force, which generates and activates life. The concept of yin and yang expresses the dual nature of all
things, the opposing but complementary forces that are interdependent on each other and must exist in equilibrium.
According to the National Certification Commission for Acupuncture and Oriental Medicine (NCCAOM), acupuncturists are licensed to
practice in 46 states and the District of Columbia.
Ayurveda Ayurveda is a 5000-year-old system of natural healing that originated in India.
Ayur means life and Veda means science of knowledge.
Assessment and treatment are based on three fundamental forces that govern the internal and external environments and determine
an individual’s constitution and overall health:
Vata (wind): energetic, creative, and adaptable. If out of balance, can be anxious, dry, thin, and have poor concentration.
Pitta (fire): intense, driven, and strong. If out of balance, can be compulsive, irritable, inflamed, and have poor digestion.
Kapha (earth): nurturing, methodical, and stable. When out of balance, can be sluggish, phlegmatic, and gain weight easily.
Mental and physical health are achieved when these forces are in balance.
Therapeutic modalities include diet, herbal and lifestyle recommendations, massage, and aromatherapy.
Massage therapy/body The philosophy behind massage therapy and body work is that there is a healing that occurs through the action of touching. Massage
work therapy became a profession in the United States in the 1940s and has grown in use over the last several decades. The key princi-
ples of body work are the importance of increasing blood circulation, moving lymphatic tissue to remove waste and release toxins,
calming the spirit, enhancing physiologic functions of body systems, and improving musculoskeletal function. This therapy also has
been widely used to reduce stress and increase energy.

United States use nonmainstream health care approaches. Worldwide, of use is significant (CRN, 2017). In children, the prevalence of
the prevalence is 12% of the adult population in Canada, 26% in the use of integrative medicine approaches did not change significantly
United Kingdom, 56% in Malaysia, and 76% in Japan (Harris et al, since 2007 except for an increase in use of yoga and a decrease in
2012). Preferences in medical care are influenced by economic and the use of nontraditional healers. Nonvitamin, nonmineral dietary
sociocultural factors. In poor countries where access to modern medi- supplements, chiropractic and osteopathic manipulations, and yoga
cine is limited, there is a heavy reliance on herbalists and traditional were the most common modalities used. The most common reasons
healers. In affluent countries, the decision to use natural therapies usu- cited were for back, neck, and musculoskeletal pain; colds; anxiety;
ally aligns with personal beliefs and preferences and is used commonly and stress.
in addition to Western medicine (Harris et al, 2012). Fig. 11.1 highlights the most common forms of integrative medi-
The use of integrative therapies has been evaluated four times in cine used by adults in the United States.
the National Health Interview Survey (NHIS)—in 2002, 2007, 2012, A significant number of Americans use some form of integrative
and most recently 2017—with a data set limited to yoga, meditation, medicine with increases seen in yoga, meditation, homeopathic
and chiropractic manipulation. In U.S. adults, the most popular inte- treatments, acupuncture, and naturopathy. Use has been shown to
grative modalities include the use of nonvitamin, nonmineral supple- be greatest among those age 55 and older, living in the West and
ments such as fish oil, glucosamine, probiotics, and melatonin (52%), Northeast of the United States, female gender, and higher socioeco-
chiropractic or osteopathic manipulation (10.3%), yoga (14.3%), nomic status and education level (CRN, 2017). By race or ethnicity, use
and meditation (14.2%) (Peregoy et al, 2014; Falci et al, 2016). of integrative approaches varies, with white adults (37.9%) and non–
The Council for Responsible Nutrition (CRN) conducts an annual Hispanic other races (37.3%) having the highest use and Hispanic
survey of over 2000 adults in the United States and reports on the (22%) and black adults (19.3%) reporting lower rates of use (Clark et al,
use of dietary supplement use. CRN reports the use of dietary supple- 2015). Among a survey of 5057 registered dietitians in the Academy of
ments in 76% of the adult population. Discrepancies exist in Nutrition and Dietetics (AND), the most common use of integrative
exact numbers between the NHIS and CRN, however the prevalence approaches includes vitamin, mineral, and other dietary supplements
190 PART II Nutrition Diagnosis and Intervention

20
17.9

15

Percent
10 8.5 8.4
6.8

5 4.1
3.0

0
Nonvitamin, Chiropractic Yoga Massage Meditation Special
nonmineral or diets
dietary osteopathic
supplement manipulation

2012 2017
15 14.3 14.2

10.3
10 9.5
9.1
Percent

5
4.1

0
Yoga Meditation Chiropractor

B
Fig. 11.1 ​A, Percentage of adults who used complementary health approaches in the past 12 months, by
type of approach: United States, 2012. (Retrieved from [Link]
B, Percentage increase by adults who used complementary approaches including yoga, meditation, and
chiropractic care between 2012 and 2017 in the United States, 2018. (Retrieved from [Link]
nchs/data/databriefs/[Link])

(such as probiotics and fatty acids) (55% to 75%), mind-body when it was renamed the National Center for Complementary and
therapies (32%), herbs (22%), and detoxification (7%) (Augustine Alternative Medicine (NCCAM). In 2015 the name was changed again
et al, 2016). to the National Center for Complementary and Integrative Health
Integrative therapies are often considered when conventional med- (NCCIH) because the use of complementary and integrative medicine
icine is not perceived as effective by the patient. Examples include in the United States is so common, it no longer warrants the term “alter-
chiropractic medicine for back pain, acupuncture for pain relief, and native.” Complementary and alternative medicine (CAM) had been the
select dietary supplementation for conditions such as macular degen- most common term used to describe the use of holistic medicine,
eration, depression, and digestive complaints. Integrative approaches although this term may be falling out of favor and is being replaced by
are also commonly used when they are supported by significant evi- complementary and integrative medicine (CIM). The NCCIH explores
dence of efficacy. The NHIS survey also suggested that integrative complementary and integrative healing practices scientifically using
medicine use increased when conventional treatments were too costly. research, training, outreach, and integration (NCCIH, 2018). There
As a result of the increased interest in integrative therapies, the continues to be an expansion of training opportunities and medical
Office of Alternative Medicine of the National Institutes of Health reimbursement for integrative therapies in the conventional medical
(NIH) was created in 1992 to evaluate their effectiveness. This office system including the U.S. Department of Veterans Affairs (VA), and many
became the twenty-seventh institute or center within the NIH in 1998, nursing and medical curricula include training in integrative medicine.
 CHAPTER 11 Food and Nutrient Delivery: Bioactive Substances and Integrative Care 191

In 2011 the Bravewell Collaborative, a philanthropic organization Herbal Medicine

that works to improve health care, published results from a national Herbal medicine has been used since the beginning of time and has a
survey on the use of integrative medicine among 29 major integrative written history of more than 5000 years. In many parts of the world, it
medical centers and programs across the United States. Top conditions is the primary source of medicine (AHG, 2019). Herbs and plants
for which the centers reported the most success in treatment included provide a large array of phytochemicals and bioactive compounds
chronic pain, gastrointestinal disorders, depression, anxiety, and stress. (plant-based chemicals and compounds) that have biologic activity
The most common interventions included nutrition, dietary supple- within the human body. Although some of the phytochemicals have
ments, yoga, meditation, acupuncture, massage, and pharmaceuticals been identified and characterized, many of them have unknown ac-
(Horrigan et al, 2012). The Academic Consortium for Integrative tions and may interact with pharmaceutical drugs (Gurley, 2012).
Medicine and Health was formed in 1999 with the goal of “transform- When herbs are used in combination with each other or in concen-
ing the healthcare system and promoting integrative medicine and trated forms (such as in a capsule or tincture), the likelihood for a drug
health for all.” Its members include over 70 academic health centers nutrient interaction (DNI) or side effect increases.
across the United States including Cleveland Clinic, Stanford, Duke, Botanical medicines are made up of a variety of plant parts includ-
Georgetown, Harvard, Johns Hopkins, Tufts, Yale, UCLA, and a num- ing leaves, flowers, stems, bark, rhizomes, and roots. They are produced
ber of state universities. The Consortium provides mentoring and in a variety of forms and are used orally and topically, including teas,
training and disseminates information about integrative approaches infusions, decoctions, extracts, and pills as shown in Box 11.2. Topical
based on rigorous scientific research (Academic Consortium for Inte- application of botanicals or nutrients such as salves and aroma therapy
grative Medicine and Health, 2018). are not classified as dietary supplements under the current regulatory
definition because they are not ingested. The Commission E Mono-
graphs on phytomedicines were developed in Germany in 1998
DIETARY SUPPLEMENTATION by an expert commission of scientists and health care professionals as
More than half of all Americans are taking some form of dietary sup- references for practice of phytotherapy, the science of using plant-
plement, and many of them may not be well informed about what they based medicines in an evidence-based way to prevent or treat illness.
are taking (Gahche et al, 2014). Historically, dietetics professionals Other useful herbal references including the American Botanical
focused their assessment, care plan, and counseling on diet or food- Council and the American Herbalists Guild are listed at the end of
related recommendations. The demand for information about dietary the chapter.
supplements from dietetics professionals is high. The 2018 Position
Paper of the AND on micronutrient supplementation calls on regis- Trends in the Dietary Supplement Industry
tered dietitian nutritionists and dietetic technicians to be reliable According to the National Health and Nutrition Examination Survey
experts with information on nutrient supplementation by keeping (NHANES) 1999-2010, the most common reasons people use dietary
up to date on issues associated with regulation, safety, and efficacy of supplements are to improve or maintain health, supplement the
dietary supplements (AND, 2018). diet, support bone health (in women), lower cholesterol, and improve
immunity (Bailey et al, 2013; Gahche et al, 2014).
Defining Dietary Supplements The industry has grown steadily for the past 30 years. Industry sales
According to the Food and Drug Administration (FDA), a dietary sup- were more than $43.5 billion in 2017 and sales are expected to continue
plement is a substance that is taken orally and is intended to add nutri- to increase (Morton, 2018). The most popular supplements according to
tional value to the diet (Food and Drug Administration, 2015). Dietary NHANES and the CRN include multivitamins and minerals (MVM),
supplements can come in many forms, including teas, tablets, capsules, vitamin D, vitamin C, omega-3 fatty acids, lutein, probiotics, and protein
powders, and liquids. A complete description can be found in Box 11.1. powders. Among children, the most common dietary supplements in-
clude multivitamins, immune support supplements like vitamin C,
omega-3 fatty acids, antacids, vitamin D, and melatonin (Quato et al,
BOX 11.1 FDA Definition of a Dietary 2018). Herbal supplement sales increased 8.5% in 2017. Herbs that ex-
Supplement perienced the strongest growth in sales include turmeric (Curcuma
longa), wheat grass (Triticum aestivum), barley grass (Hordeum vulgare),
Intended to be a supplement to the diet
elderberry (Sambucus nigra), fenugreek (Trigonella foenum-graecum),
Intended to be taken by mouth; this excludes other routes of administration,
echinacea (Echinacea spp.), and cranberry (Vaccinium macrocarpon),
such as intranasal, transdermal, and suppository
(Smith et al, 2018).
Contains one or more dietary ingredients, including the following:
Macronutrients (protein, carbohydrates, fats) Multivitamin Efficacy
Vitamins and minerals
Most people take an MVM to increase nutrient levels in the diet or
Herbs and botanicals
fill perceived gaps in nutrition. Dietary surveillance data from the
“Other” dietary substances that are either grandfathered in or are approved as
National Center for Health Statistics (NCHS) and NHANES reveal
New dietary ingredients (NDIs), such as:
that most adults and children in the United States are not meeting
Phytochemicals (such as curcumin from Turmeric)
dietary guidelines and are underconsuming dark greens, orange veg-
Bee pollen
etables, legumes, and whole grains (Bowman et al, 2018). Total nutri-
Probiotics
ent intakes for vitamin D, vitamin E, calcium, vitamin A, vitamin C,
Glandulars (products made from dessicated animal glands)
and magnesium have been found to be significantly below the esti-
Some hormones, including melatonin and DHEA
mated average requirement (EAR), and less than 3% of the popula-
Does not contain any unapproved ingredients, such as:
tion is meeting the adequate intake (AI) for potassium (Drake and
Thyroid hormone, cortisol, estrogen, progesterone, or testosterone
Frei, 2018).
Pathogenic bacteria
Use of multivitamins and minerals has been shown to improve
Human tissue
micronutrient status among adults and children (Bailey et al, 2012;
192 PART II Nutrition Diagnosis and Intervention

found evidence that they reduce chronic disease or prevent early death
BOX 11.2 Botanical Formulations
with the exception of some forms of cancer and potentially cardiovas-
Type Form cular disease, especially for long-term users of MVMs (Fortmann et al,
Bulk Herbs 2013; Blumberg et al, 2018). Two trials, the Supplementation in
Sold loose to be used as teas, in cooking, and in Vitamins and Mineral Antioxidants Study ([Link]) and the Phy-
capsules; rapidly lose potency; should be stored in sicians’ Health Study II (PHS-II), found a small reduction in cancer
opaque containers, away from heat and light. incidence for men only after 12 ½ years ([Link]) and 8 years
Beverages (PHS-II) of supplementation (Fortmann et al, 2013; Gaziano et al,
Teas Beverage weak in concentration; fresh or dried 2012). More recently, analysis of male physicians in the Physicians’
herbs are steeped in hot water and strained Health Study I cohort who reported taking an MVM for more than
before drinking. 20 years showed a lower risk of cardiovascular events. In a nationally
Infusions More concentrated than teas; steep fresh or dried herbs representative sample of women from NHANES, those who took
for approximately 15 min to allow more of the active an MVM for more than 3 years had lower cardiovascular mortality
ingredients to be extracted than for teas. A cold although the results were deemed nonsignificant when the results
infusion is made by steeping an herb over time in a were fully adjusted for confounding variables (Rautiainen et al, 2016;
cold liquid. Bailey et al, 2015). Trials looking at cognitive decline and all-cause
Decoctions Most concentrated of the beverages, made by simmering mortality have not shown statistically significant incidence of harm or
the root, rhizome, bark, or berries for 30-60 min to benefit (Fortmann et al, 2013). Chronic diseases are complex and usu-
extract the active ingredients. ally have multifactorial causes. Studying the effect of an MVM on
Extracts nutrient intake and overall health is a difficult undertaking. Almost all
Herbs are extracted with an organic solvent to dissolve Americans are taking in supplemental forms of nutrients via fortified
the active components; forms a concentrated form of foods, which complicates efforts to quantify the impact of taking an
the active ingredients. Standardized extracts MVM supplement. In observational trials, people take a variety of
concentrate a specific constituent(s) of an herb. MVMs with differing compositions and potencies. People who
Removal of the solvent creates a solid extract. self-select to take an MVM are usually healthier and have better
Tinctures Extract in which the solvent is alcohol, glycerine, honey, diets, suggesting that MVMs may not be helpful for most well-
or occasionally vinegar. Ratios are listed as nourished people. A few long-term RCTs evaluated the merits of
herb:quantity of solvent. A 1:1 tincture is equal parts MVMs, and the results have been population or gender specific and
herb and solvent. not generalizable to the entire U.S. population (Fortmann et al, 2013).
Glycerites Extract in which the solvent is glycerol or a mixture of MVMs may have efficacy based on assessment of individual needs,
glycerol and water; more appropriate for children than especially with the advent of nutrigenomics and personalized nutri-
an alcohol based tincture. tion, but are not generally useful for all people. In those who do
Salve An infusion of herbs in oil and beeswax that is used supplement with MVMs, there is little evidence for harm, however
topically. This preparation is not considered to be a assessment should include a risk for exceeding upper limits on nutri-
dietary supplement under DSHEA. ents, especially when multiple supplements are taken at the same time
Pill Forms (Blumberg et al, 2018).
Pills should be taken with at least 8 oz of water to avoid
leaving residue in the esophagus. Antioxidant Supplements
Capsules Herbal material is enclosed in a hard shell made from Oxidative stress is implicated in a variety of disease states, and many
animal-derived gelatin or plant-derived cellulose Americans take antioxidant supplements. A Cochrane review of
(vegetarian caps). 78 RCTs with 296,707 participants found that all-cause mortality was
Tablets Herbal material is mixed with filler material (excipients) increased slightly with regular antioxidant use. The effect was strongest
to form the hard tablet; may be uncoated or coated with beta carotene in smokers, and high-dose vitamin E and vitamin
with starches and polymers. A. Vitamin C and selenium were not found to increase mortality but
Lozenges Also called troches; method of preparation allows the also did not improve longevity (Bjelakovic et al, 2012). Antioxidant
active components to be readily released in the mouth supplements may be beneficial, however, for prevention of age-related
when chewed or sucked. macular degeneration (AMD). In the Age-Related Eye Disease Study
Soft gels Soft capsule used to encase liquid extracts such as fatty (AREDS), high-dose vitamin C (500 mg), vitamin E (400 IU), beta
acids or vitamin E. carotene (15 mg), and zinc (80 mg) had a significant reduction in the
Essential oils Fragrant, volatile plant oils; used for aromatherapy, risk of developing AMD after taking the antioxidant supplements for
bathing; concentrated form and not to be used 6.3 years. The effects were still present after a 10-year follow-up (Chew
internally unless specifically directed (such as enteric- et al, 2013). For the majority of people, it is probably best to get anti-
coated peppermint oil capsules). oxidants and phytonutrients by eating a variety of plant-based foods,
including fruits, vegetables, herbs, spices, nuts, seeds, legumes, and
whole grains.

Blumberg et al, 2017). Unfortunately, increased nutrient intake has not Potentially At-Risk Populations
translated into reduced risk of chronic disease in people without overt Although dietary supplement use is most common among people who
nutrient deficiencies. Research reviews by the NIH State of Science are least likely to have a nutrient deficiency, the AND has identified
Panel and the U.S. Preventive Services Task Force have evaluated ob- several populations and life cycle stages that potentially could benefit
servational and randomized controlled trials (RCTs) of more than from dietary supplements (AND, 2018). Table 11.3 outlines potentially
400,000 people using single or paired vitamins or MVM and have not at-risk populations. Clinicians should be aware of these at-risk
 CHAPTER 11 Food and Nutrient Delivery: Bioactive Substances and Integrative Care 193

TABLE 11.3 Populations Potentially at Risk for Nutrient Deficiencies

Nutrients of Concern that Could Potentially Be Corrected
At-Risk Population or Life Cycle Stage by Supplementation
Those living in poverty (especially children) Iron, calcium, magnesium, folate, vitamins A, B6, C, D, and E
Those taking oral contraceptives Zinc, folic acid, B6, and B12
Adolescent females Iron and calcium
Pregnancy Iron and folic acid
Older adults B12 and vitamin D, multiple micronutrients
Those following calorie-restricted weight loss diets Multiple nutrients
People with dark pigmented skin Vitamin D
People with malabsorption (inflammatory bowel disease, gastric bypass) Multiple nutrients
Those who avoid food groups due to allergy or preference including Multiple nutrients, iron, zinc, calcium, B12
strict vegetarians and vegans
Those with genetic predisposition to nutrient deficiencies (i.e., MTHFR Folate, B12, vitamin D. Use of nutrigenomic testing is still an emerging science.
or vitamin D receptor mutations)
Those with advanced macular degeneration (AMD) Vitamin C, vitamin E, zinc, copper, lutein, and zeaxanthin
Smokers Vitamin C
Those with alcoholism Folate and thiamin
People taking medications that deplete nutrients Multiple nutrients
Adapted from the Academy of Nutrition and Dietetics. Position of the Academy of Nutrition and Dietetics: Micronutrient Supplementation. J Acad
Nut Diet 118(11):2162-2173, 2018.

subgroups and complete a nutrition assessment to determine the need

for supplementation on an individual basis if nutrition status cannot
be improved by dietary changes alone.
Supplement Facts
Serving Size 1 Capsule

DIETARY SUPPLEMENT REGULATION Amount Per % Daily

Capsule Value
Dietary supplements are regulated by two government agencies, the
FDA, which oversees safety concerns, and the Federal Trade Commis- Calories 20
sion (FTC), which oversees advertising, label, and health claims. Before Calories from Fat 20
1994, dietary supplements existed in limbo under the general, but Total Fat 2 g 3%*
unspecified, regulation of the FDA. The Dietary Supplement Health Saturated Fat 0.5 g 3%*
and Education Act of 1994 (DSHEA) defined dietary supplements Polyunsaturated Fat 1 g †
under the category of food and explicitly removed them from consid- Monounsaturated Fat 0.5 g †
eration as drugs or dietary additives. This was seen as a victory to the
Vitamin A 4250 IU 85%
dietary supplement industry and consumers; they had become accus-
tomed to open access in ability to manufacture and purchase dietary Vitamin D 425 IU 106%
supplements without many restrictions.
Omega-3 fatty acids 0.5 g †
Dietary supplement regulation set forth by DSHEA includes the
following (NIH, 1994):
• Generally recognized as safe (GRAS) status to all supplements * Percent Daily Values are based on a 2,000 calorie diet.
† Daily Value not established.
produced before October 15, 1994. This allows manufacturers to
continue to sell all of the products that were on the market at the Ingredients: Cod liver oil, gelatin, water, and glycerin.
time DSHEA was passed. Any company that introduces a new Fig. 11.2 ​A dietary supplement facts label per Food and Drug Adminis-
dietary supplement must send notification and safety information tration regulation as defined under the Dietary Supplement Health
to the FDA 75 days before selling the supplement. Education Act.  (From [Link]
• A supplement facts panel that defines how ingredients must be documents/image/[Link].)
listed on the label. See Fig. 11.2 for an example of a dietary supple-
ment label.
• Structure function claims vs. health claims: Supplement companies evaluated by the Food and Drug Administration. This product is
are no longer allowed to list disease states or make specific health not intended to diagnose, treat, cure, or prevent any disease.” Op-
claims on a dietary supplement label. A structure function claim ponents of DSHEA feel that structure function claims are too
allows for a description that includes a structure or function of the similar to drug claims and encourage dietary supplements to be
body or a stage of life. “Supports strong bones” is an allowable used like drugs. By contrast, a health claim can mention a disease
structure function claim; “Prevents osteoporosis” is not. The label state as long as it has met the significant scientific agreement stan-
must also include the disclaimer, “This statement has not been dard of the FDA and can exist on foods and dietary supplements.
194 PART II Nutrition Diagnosis and Intervention

For example, “soluble fiber from foods such as oat bran, as part of recalled between 2009 and 2012, 85% of the sports supplements, 67%
a diet low in saturated fat and cholesterol, may reduce the risk of weight loss, and 20% of sexual enhancement products were still
of heart disease.” The FDA has approved only a limited number of available and still contained the banned ingredient (Cohen et al, 2014).
health claims. In December 2006 the Dietary Supplement and Nonprescription
• Disseminating product literature: Dietary supplement manufactur- Drug Consumer Protection Act was signed into law, requiring manda-
ers and retailers are no longer able to display product information tory reporting by manufacturers and retailers of known serious
or technical data sheets next to products because they can mislead adverse events (AEs) related to dietary supplement and over-the-
consumers and make dietary supplements appear to be drugs. counter (OTC) medications. Serious AEs include a life-threatening
• Because a wide variety of dietary supplements are available, in- event, incapacitation, hospitalization, a birth defect, or death. These
cluding some hormones and megadose vitamins, it is up to con- must be reported to the FDA MedWatch website and can be filed by an
sumers to be educated about the dietary supplement they choose individual, a health care provider, or an industry representative. In ad-
to consume. The NIH founded the Office of Dietary Supplements dition, supplement manufacturers are required by law to have contact
(ODS) in 1994 to fund research and disseminate credible infor- information on supplement bottles. AE reports are forwarded to the
mation on dietary supplements to consumers. On this govern- Center for Food Safety and Applied Nutrition, where they are further
ment website, consumers can find basic consumer information, evaluated by qualified reviewers (FDA, 2013). Health care providers
technical data sheets about dietary supplements and herbs, and and consumers are not mandatory reporters under the law but are
FDA warnings. strongly encouraged to report AEs.
• Good manufacturing procedures (GMPs) were adopted in 2007 Between 2008 and 2011 the FDA and poison control centers re-
and went into full enforcement in 2010. According to the GMPs, ceived almost 13,000 AE reports related to dietary supplements. Of
manufacturers of dietary supplements must meet minimum stan- those, 71% were considered serious AEs. During that same time, the
dards for production and are subject to random audits. The GMPs FDA logged 2.7 million adverse drug events, of which 63% were con-
regulate the design and construction of manufacturing plants, sidered serious (Government Accountability Office, 2013). The 2013
maintenance and cleaning procedures, manufacturing procedures, Annual report of the American Poison Control Centers revealed 1692
quality control procedures, testing of materials, handling of con- deaths due to drugs and zero deaths due to dietary supplements. Less
sumer complaints, and maintaining records (FDA, 2010). than 1% of Americans experience AEs related to dietary supplements
Under DSHEA, dietary supplements are regulated only for safety and the majority are classified as minor (Brown, 2017). It is estimated
and not for efficacy. Manufacturers are beholden to follow the regula- that many AEs from taking supplements are not being reported or are
tory laws governing dietary supplements; however, they do not have to not being reported correctly. Common barriers from consumers
send any premarket notification to the FDA except for structure func- include downplaying the significance, not knowing where or how to
tion claims and safety documentation for new dietary ingredients report, and embarrassment. After nine years of tracking (2004 to
(NDIs) that were not used before 1994. The FDA randomly inspects 2013), the Centers for Disease Control and Prevention (CDC)
more than 300 dietary supplement manufacturers per year. According released a report indicating that an estimated 23,000 emergency
to the Natural Products Insider via information obtained through the department visits per year could be attributed to dietary supple-
Freedom of Information Act (FOIA), in fiscal year 2018, 75 inspections ments. Among young adults ages 20 to 34, the most common
(,24% of inspections) resulted in GMP violations and companies supplements causing AEs were for weight loss and energy (ergogenic
were cited by the FDA. The most common noncompliance issues were aids) and the most common symptoms were tachycardia, chest pain,
failure to test products for identity, potency, and purity (Long, 2018). and palpitations. For adults 65 and older, AEs were mostly attributed
The FDA is increasing its auditing program every year. With repeated to choking on micronutrient pills. Twenty percent of dietary supple-
audits, many of the noncompliant companies will be forced to comply ment related emergency visits were for unsupervised children
or shut down, which will help ensure increased safety in the industry. who ingested dietary supplements (Geller et al, 2015). Health care
For now, health care providers should recommend dietary supple- providers who wish to stay abreast of alerts from the FDA can sub-
ments only from reputable companies. The FDA does not publish data scribe to the MedWatch email list on the FDA website. The ODS
on which companies pass or do not pass inspections. This information website is another resource for information about current warnings
can only be obtained via the FOIA or by looking on the FDA warning and recalls as well as consumer tips for buying and taking dietary
letters database under the company name. supplements safely.
Botanical supplements are increasing in popularity, and some have
Ensuring Dietary Supplement Safety the likelihood for producing AEs, especially when taken in combina-
Under DSHEA, the FDA bears the burden of proving a supplement is tion products and in concentrated form. Most of the common herbs
unsafe. This can be a challenging task once a product is released onto used in the United States do not pose a great risk for a drug nutrient
the market. To date, only two dietary supplements have been banned interaction (DNI). Of the herbs most commonly used, St. John’s wort
by the FDA over safety issues, Ephedra sinica in 2004, and dimethyl- is the most problematic and has been shown to reduce efficacy of many
amylamine (DMAA) in 2013. Both have been linked to cardiovascular drugs, including antiretrovirals for HIV, antirejection medications for
toxicity and death. The most common supplements with health and organ transplants, oral contraceptives, cardiac medications, chemo-
safety concerns are those used for weight loss, performance enhance- therapy, and cholesterol medications. Two other herbs have been
ment (ergogenic aids), and sexual dysfunction (FDA, 2018). These shown to have a high risk for DNI, including goldenseal (Hydrastis
supplements have the highest risk of contamination and adulteration canadensis) and black pepper (Piper nigrum), although black pepper is
with unapproved dietary ingredients and pharmaceutical drugs, espe- only a problem in supplemental form and not in amounts commonly
cially when purchased from obscure retailers and on the Internet. In- found in food (Gurley et al, 2012).
ternet sales of dietary supplements is one of the fastest-growing retail In recent years the ODS has worked collaboratively with several
markets and is also the hardest to regulate. Consumers can often find organizations and experts to develop a Dietary Supplement Label
banned supplements easily on the Internet. In a 2014 study, researchers Database of dietary supplements used in the United States. Because
found that when products are recalled or banned by the FDA, a sig- the database provides specific information on the nutrient, herbal, or
nificant number of them are still available online. Of 274 supplements other constituents contained in a supplement, it allows clinicians to
 CHAPTER 11 Food and Nutrient Delivery: Bioactive Substances and Integrative Care 195

WHAT IS THE
INTENDED
USE?

Applied to Used to Consumed Ingested to Ingested to

body for diagnose, for its taste, affect structure supplement
cleansing, cure, mitigate, aroma, or or function the diet
beautifying, treat, or prevent nutritive of body
or altering disease value
appearance

COSMETIC DRUG CONVENTIONAL DIETARY FUNCTIONAL

FOOD SUPPLEMENT FOOD

Fig. 11.3 ​Use of dietary supplementation in clinical practice requires use of a credible resource for evaluation
and application.  (From Thomson CA, Newton T: Dietary supplements: evaluation and application in clinical
practice. Topics Clin Nutr 20(1):32, 2005. Reprinted with permission.)

assess more accurately the appropriate use of select supplements by Quality Issues in Dietary Supplements
their patients (Fig. 11.3). The database includes dietary supplement Not all dietary supplements are high quality. As discussed previously,
label information for more than 76,000 dietary supplement products, many manufacturers are not in full compliance with DSHEA, which
including the ingredients, daily values, and structure and function means many substandard and contaminated and adulterated products
claims. The ODS offers Supplement Fact Sheets containing infor- are on the market. Many of the popular brands in health food stores
mation about dietary supplements that is linked to PubMed, and major retail outlets are likely safe. Products bought off the Internet
allowing clinicians and consumers to access to peer-reviewed informa- and from obscure retailers may be adulterated and/or may not meet
tion on use in human trials, AEs associated with use, and information label claims. What determines quality in a supplement must go beyond
regarding the mechanism of action. The Natural Medicines Compre- the safety issues to address the quantity, formulations, and quality of
hensive Database and Consumer Lab (subscriptions needed) offer all ingredients used.
similar information.
Quantity of Ingredients
Third Party Certification Many MVMs contain megadoses of nutrients, which greatly exceed
The FDA and FTC have primary jurisdiction for ensuring dietary the RDA and may or may not be appropriate for each individual
supplements are safe and do not have misleading advertising. With consumer. Some individuals may benefit from high doses of certain
approximately 85,000 products on the market, this is a daunting nutrients because of genetic variations in enzyme function or other
task. Because supplement manufacturers are audited randomly, pharmacologic effects of megadoses. Examples include increased need
it is not easy for consumers to know whether a company is truly fol- for folate with an MTHFR gene variant or reduction in triglycerides
lowing GMPs and their products are free from adulteration. Several with megadoses of niacin (Ames et al, 2002; Boden et al, 2014).
private companies offer third party certification in the supplement It is important to assess for upper limits, especially when patients
industry. Consumer Lab is a well-known and affordable subscription- are taking multiple sources of nutrients. Most water-soluble vitamins
based company that randomly pulls supplements from store shelves to do not have overt toxicity at high doses with the exception of niacin
test them for potency, identity, and purity. Subscribers to the (flushing, prickly heat, and liver irritation in some people) and pyri-
Consumer Lab website are able to access reports that reference specific doxine (reversible neuropathy). Fat-soluble vitamins can become toxic
brands. The U.S. Pharmacopeia (USP), the National Sanitation more quickly, such as vitamin A (hepatotoxicity and teratogenicity)
Foundation (NSF), and the Therapeutic Goods Association (TGA) and vitamin D (nephrolithiasis, calcification of soft tissue). Often vita-
each certify supplement companies for compliance with federal GMPs. min A is listed in its provitamin form, beta carotene, which does not
Once verified, companies can display a stamp on their supplement pose the same health risks as retinol at high doses.
labels that signifies the products have been third party certified. In Minerals can become toxic more easily than vitamins, so they often
addition, NSF offers a “Certified for Sport” certification for supple- are not formulated using megadoses. In some cases, people may take a
ments that are used by competitive athletes to ensure they are not megadose of a mineral for a limited time, such as zinc for the common
contaminated with illegal substances. cold. To ensure patient safety, it is important to coordinate care with a
The Codex Alimentarius Commission (Codex) is an agency with physician when a patient is taking a megadose of a mineral. Although
international significance. It was created in 1963 by two U.N. organiza- it is not a megadose, the FDA limits potassium content in dietary
tions, the Food and Agriculture Organization and the World Health supplements to 99 mg because of the prevalence of chronic kidney
Organization, to protect the health of consumers and to ensure fair disease. In patients with end stage kidney disease, high potassium
practices in international food trade. Codex participants work on the levels can cause cardiac arrhythmia or arrest.
development of food standards, codes of practice, and guidelines for
products such as dietary supplements. Codex standards and guidelines Formulations
are developed by committees from 180 member countries, where they Dietary supplements come in many formulations, including capsules,
voluntarily review and provide comments on standards at several tablets, gels, chewables, liquids, and powders. The form a consumer
stages in the development process. selects has to do with convenience, preference, and affordability.
196 PART II Nutrition Diagnosis and Intervention

Supplement powders can be added easily to foods and beverages, but including cyanocobalamin are equally effective at treating B12 defi-
most have added sugars to increase palatability. Chewable and liquid ciency (Obeid et al, 2015).
supplements often are missing multiple nutrients to increase taste appeal, Vitamin E can be made synthetically or extracted naturally from
so it is important to assess the label to ensure it meets the patient’s needs. soybean oil, sunflower oil, or other vegetable oils. Natural vitamin E
Tablets tend to be more compressed than capsules and require a (d-alpha tocopherol) is more expensive but has a greater bioavailabil-
fewer number of pills to achieve the optimal dosage. Capsules tend to ity than synthetic vitamin E (dl-alpha tocopherol) (Landvik, 2004;
be easier to swallow but less concentrated than tablets. Gelatin capsules AND, 2018). High-quality vitamin E products usually contain mixed
may not be suitable for vegetarians. Some companies make vegetarian tocopherols and tocotrienols in addition to the d-alpha tocopherol,
capsules out of vegetable cellulose to accommodate vegetarian con- which is thought to mimic more closely what one would get from
sumers. Other nutrient forms that may not be suitable for vegetarian eating a food source of vitamin E. Tocotrienols have been shown to
clients include cholecalciferol (often from fish oil or lambswool) and possess potent antioxidant and antiinflammatory qualities, although
vitamin A/retinol (also usually from fish oil). Vegetarian formulations dietary sources such as nuts, seeds, and plant-based oils may be supe-
usually contain ergocalciferol and beta carotene as alternatives. Some rior to dietary supplements (Peh et al, 2016).
manufacturers produce cholecalciferol from lichen and mushrooms,
which are vegetarian sources. Minerals
Chelated minerals bound to an amino acid or a Krebs cycle inter-
Excipients mediary are considered the most easily absorbed form of a mineral
Excipients are extra ingredients added to dietary supplements to in- supplement, especially in specific populations such as older adults,
crease bulk, mask “off flavors,” add color, and improve compressibility preterm infants, people with low stomach acid, and those with
and flow through machinery. To assess whether a dietary supplement is compromised digestion including inflammatory bowel disease
right for an individual, it is important to consider the quality of the ex- (IBD) and celiac disease but may not be better than other forms in
cipients used. Some contain allergens and/or potentially unfavorable healthy young people (Chermesh et al, 2006). Examples of chelated
ingredients, such as wheat starch, lactose, hydrogenated oils, artificial minerals include citrate, malate, bisglycinate, succinate, aspartate,
colors. When choosing a dietary supplement, it is important to read the and picolinate. Chelated minerals are less concentrated that ionic
label for quantity and quality of active ingredients and excipients. minerals and therefore more pills will often be needed to obtain the
same dose. Chelated minerals can also be more expensive. Ionic
Vitamins mineral preparations such as carbonates and oxides should
Most vitamins in dietary supplements are similar across brands with be taken with food, especially protein, to increase absorption
the exception of B6 (pyridoxine), B12 (cyanocobalamin), folate (folic (Straub, 2007).
acid), and vitamin E. Some formulations contain active, methylated, or
phosphorylated forms of these nutrients such as in active B6: pyridoxal ASSESSMENT OF DIETARY SUPPLEMENT USE
59-phosphate, active B12: methylcobalamin or adenosylcobalamin, and
active folate: methyltetrahydrofolate. Individuals with genetic poly-
IN PATIENTS
morphisms, nervous system disorders, increased oxidative stress, or Health care professionals should be aware that patients often do not
impaired digestion may benefit from the increased bioavailability of report their use of botanicals or other dietary supplements. Therefore
these nutrients; however, research is limited on their widespread need practitioners must inquire specifically about the use of supplements by
and efficacy. In addition, the active forms tend to be more expensive their patients. To facilitate disclosure, health care providers, including
(Head, 2006; Hendren, 2013). A review published in 2015 refutes the RDNs should approach patients in an open-minded, nonjudgmental
necessity of coenzyme forms of cobalamin, finding that all forms, manner. Key questions to ask are summarized in Box 11.3. Ideally,

BOX 11.3 Evaluating Dietary Supplement Use: The Patient–Health Care Provider Information
Exchange
Ask • Health status and health history—include lifestyle habits (e.g., smoking,
• What dietary supplements are you taking (type: vitamin, mineral, botanical, alcohol, physical activity level)
amino acid, fiber, including brand and dose)? • Biochemical profile, laboratory data
• Why are you taking these dietary supplements? Include review of patient’s • Prescribed and over-the-counter (OTC) medications
medical diagnosis and symptoms for reasons why they may be taking supple- • Clinical response to supplements
ments (e.g., osteoarthritis, heart disease, high blood pressure, premenstrual • Adverse events, symptoms
syndrome [PMS], fatigue).
• How long have you been taking these dietary supplements? Educate
• What dose or how much are you taking? For each, include supplement form • Scientific evidence of benefit and effectiveness
and manufacturer. • Potential interaction with foods, nutrients, and medications or other dietary
• With what frequency are you taking each supplement? supplements
• Where were the supplements purchased (e.g., health food store, Internet, • Appropriate dose, brand, and chemical form; duration of supplementation;
health care provider)? appropriate follow-up
• Who recommended the supplement (e.g., media, physician, nurse, dietitian, • Quality of products, manufacturers, good manufacturing practices (U.S.
integrative medicine practitioner, friend, family)? Pharmacopeia [USP], Consumer Labs)
• Mechanism of action of the primary active ingredient
Evaluate • Appropriate storage of the dietary supplement
• Dietary intake (including intake of fortified foods and beverages, and nutri- • Administration instructions: With or without food? Potential food-supplement
tional and sports bars) interactions?
 CHAPTER 11 Food and Nutrient Delivery: Bioactive Substances and Integrative Care 197

BOX 11.3 Evaluating Dietary Supplement Use: The Patient–Health Care Provider Information
Exchange—cont'd
• Awareness and reporting of any side effects or adverse events, symptoms • Record batch number from bottle in case of an adverse event.
• Recommend necessary dietary changes to support needs. Food should • Record patient perception and expected level of compliance.
come first. • Monitor efficacy and safety, including health outcomes and adverse effects.
• Record medication-supplement or supplement-supplement interactions.
Document • Plan for follow-up.
• List specific supplements and brand names of each supplement being
taken.
From Practice Paper of the American Dietetic Association: Dietary supplements, J Am Diet Assoc 105(3):466, 2005. Reprinted with permission.

BOX 11.4 Dietary Supplements that Affect BOX 11.5 International Dietetics and
Blood Clotting and Should Be Discontinued Nutrition Terminology (IDNT) that Applies
10 to 14 Days Before Surgery or Certain to the Documentation of Dietary Supplement
Medical Tests Use Among Patients
Ajoene, birch bark, cayenne, Chinese black tree fungus, cumin, evening prim- Assessment Terminology: Food and Nutrient Intake, Medication and
rose oil, feverfew, garlic, ginger, Ginkgo biloba, ginseng, grapeseed extract, Complementary and Alternative Medicine Use and Knowledge, Beliefs and
milk thistle, omega-3 fatty acids, onion extract, St. John’s wort, turmeric, vita- Attitudes
mins C and E Diagnosis Terminology: Inadequate bioactive substance intake (NI-4.1), Excessive
bioactive substance intake (NI-4.2), Increased nutrient needs (NI-5.1), Decreased
Reference: American College of Surgeons. College of Education: Med-
ication and Surgery Before Your Operation (website): [Link]
nutrient needs (NI-5.4), Imbalance of nutrients (NI-5.5), Less than optimal intake
org/patienteducation/[Link]. of types of fats (NI-5.6.3), Less than optimal intake of types of proteins or amino
acids (NI-5.7.3), Inadequate fiber intake (NI-5.8.6), Inadequate vitamin intake
(specify) (NI-5.9.1), Excessive vitamin intake (specify) (NI-5.9.2)
Inadequate mineral intake (specify) (NI-5.10.1), Excessive mineral intake (spec-
patients should be encouraged to bring all of their dietary supplements ify) (NI-5.10.2), Predicted suboptimal nutrient intake (specify) (NI-5.11.1),
and medications into the clinic to be evaluated. In this way the health Predicted excessive nutrient intake (specify) (NI-5.11.2), Impaired nutrient
care provider can review doses (including those above the tolerable utilization (NC-2.1), Altered nutrition related laboratory values (specify) (NC-
upper limit [UL]), forms, frequency of use, rationale for use, side 2.2), Food-medication interaction (NC-2.3), Predicted food-medication inter-
effects, and the patient-perceived efficacy of each supplement (AND, action (NC-2.4), Food and nutrition related knowledge deficit (NB-1.1), Un-
2018). This should be done on a regular basis. It is particularly supported beliefs and attitudes about food or nutrition related topics
important that dietary supplement use be reviewed before surgery be- (NB-1.2), Limited adherence to nutrition related recommendations (NB-1.6)
cause some dietary supplements and botanicals alter the rate of blood Intervention Terminology: Vitamin and mineral supplements (specify) (ND-
coagulation. Box 11.4 provides specific recommendations regarding 3.2), Bioactive substance management (specify) (ND-3.3), Nutrition related
the discontinuation of dietary supplements before surgery to avoid medication management: Nutrition related complementary/alternative
complications associated with prolonged bleeding time. In addition, medicine (ND-6.3), Nutrition education (specify) (E-1), Nutrition counseling
patients on blood-thinning medications may have to be monitored for (specify) (C-1), Collaboration and referral of nutrition care (RC-1)
a potential interaction with these supplements (American College of
Surgeons, 2012).
For assessing patients for dietary supplement use using the NCP,
potential diagnosis and intervention codes are shown in Box 11.5.
include the supplement name, dosage, form, duration of use, and a
Recommendation and Sale of Dietary Supplements short description of supporting evidence. Each provider is responsible
Many health care professionals are uncomfortable recommending to cross-check for contraindications and potential DNIs and docu-
dietary supplements. Clinical guidelines for recommending and selling ment any risks in the patient’s medical chart. See Box 11.6 for guide-
dietary supplements have been published previously by the Academy lines for choosing dietary supplements and botanical products and
of Nutrition and Dietetics (Thompson et al, 2002). Dietitians and Box 11.7 for information about usage, dosage, and safety of some of
nutritionists who recommend dietary supplements must take the the most commonly used dietary supplements.
initiative to develop their knowledge, skills, and resources to provide
accurate and safe recommendations. The AND has developed The Resources for Clinicians
Academy Scope of Practice Decision Tool: A Self-Assessment Guide for As awareness of dietary supplement use expands within the health care
dietetics providers; it is available through the AND website. It can be community, the number of evidence-based resources available to clini-
used to assess competence and scope of practice as defined by training, cians is also growing considerably. Clinicians should have access to
place of employment, and state of residence. It is advisable to use this online and print resources that are updated at regular intervals.
tool before beginning any new practice, including recommending or Resources that provide references to the original research are prefera-
selling dietary supplements. ble. A list of evidence-based resources can be found at the end of the
When recommending dietary supplements to clients, clinicians chapter. In addition, accessing available medical literature is advised,
should use an evidence- or science-based approach and document given that there are a growing number of studies being published in
thoroughly in the patient’s medical chart. Documentation should peer-reviewed literature.
198 PART II Nutrition Diagnosis and Intervention

BOX 11.6 Guidelines for Choosing Dietary Supplements and Botanical Products
• Ensure the supplement is appropriate for the individual patient based on state • Use the dietary supplement label to obtain important information, including
of health, dietary deficiency, and scientific evidence. the following:
• Consider multiple sources of dietary supplements including fortified foods, • Product identity (including scientific or botanical names), form, and
bars, cereals, and beverages to ensure patients are not exceeding safe intake dosage
limits. • Allergy information in case the patient has a dietary restriction. Excipients
• Check for potential drug-nutrient interactions and be aware of side effects (inactive ingredients) are often the source of allergens or unwanted ingre-
and contraindications. For example, fish oil can reduce blood clotting in high dients.
doses and antioxidant supplements can inhibit the effects of some chemo- • A lot number, which is helpful if problems arise because it allows
therapy drugs. the product to be tracked through each stage of the manufacturing
• Investigate the quality of the manufacturer to ensure a quality product. Look process.
for companies that have third party certification (National Sanitation Founda- • An expiration date
tion [NSF], U.S. Pharmacopeia [USP]), or well-known companies with a long- • After determining that a manufacturer and its product meet these standards,
standing reputation for quality. Check Consumer Labs or the Food and Drug compare prices among products of similar quality. Prices can vary widely.
Administration (FDA) warning letters website for documented problems.
National Institutes of Health, Office of Dietary Supplements. Dietary Supplements: What You Need to Know. [Link]
[Link]. Academy of Nutrition and Dietetics. Position of the Academy of Nutrition and Dietetics: Micronutrient Supplementation. J Acad Nut Diet
118(11):2162–2173, 2018.

BOX 11.7 Popular Dietary Supplements and Their Efficacy

Potential
Supplement Benefits Dosage Contraindications Quality Considerations
Vitamins
Vitamin B6 Effective for hereditary Most supplemental doses are Doses up to 200 mg/day appear Available as pyridoxine and
sideroblastic anemia, 5-50 mg/day. 25 mg every to be tolerated by most pyridoxal 59-phosphate
pyridoxine-dependent 8 hours for pregnancy induced people, although high doses (coenzyme form).
seizures; Likely effective for nausea and vomiting. Doses can cause hypotension and
hyperhomocysteinemia, age- up to 200 mg/day have been reversible neuropathy.
related macular degeneration, used for carpel tunnel, but
hypertension, calcium oxalate close monitoring is
kidney stones, pregnancy recommended.
induced nausea and vomiting
Vitamin B12 Effective for pernicious anemia Doses in supplements are often Most risk is associated with Available as cyanocobalamin,
and B12 deficiency. Likely in megadoses due to lack of intravenous forms, not oral methylcobalamin and
effective for toxicity. Can be taken orally forms. People with pernicious adenosylcobalamin (coenzyme
hyperhomocysteinemia; and injected. Common dosage anemia will not benefit from forms). Active form may be
possibly effective for age- range is 2.4-1000 mcg/day. oral dosing. beneficial for those with genetic
related macular degeneration polymorphisms; however all
forms of B12 have been found
effective for correcting B12
deficiency.
Vitamin C Effective for scurvy; likely Doses vary widely but usually Safe at lower doses and in Mineral ascorbates (buffered
effective for iron absorption range from 100-2000 mg/day. amounts found in foods. vitamin C) or Ester C® may be
enhancement; possibly Use divided doses for enhanced Higher doses can cause better tolerated (less
effective for age-related absorption. diarrhea and gastrointestinal gastrointestinal [GI] distress)
macular degeneration, cancer cramping. Greater than than ascorbic acid for some
prevention, common cold 500 mg is contraindicated for people.
prevention and treatment, those who have a history of
complex regional pain calcium oxalate kidney
syndrome, hypertension, stones.
osteoarthritis, sunburn
 CHAPTER 11 Food and Nutrient Delivery: Bioactive Substances and Integrative Care 199

BOX 11.7 Popular Dietary Supplements and Their Efficacy—cont'd

Potential
Supplement Benefits Dosage Contraindications Quality Considerations
Vitamin D Effective for familial Dose is usually based on Exceeding the UL and elevated Cholecalciferol (D3) is the most
hypophosphatemia, individual serum levels and serum concentrations are common supplement and is
hypoparathyroidism, can vary from person to associated with calcification usually sourced from fish or
osteomalacia, psoriasis, person. Optimal serum level is of soft tissues (damage to the sheep (lanolin), lichen, or
renal osteodystrophy, and considered to be 30-50 nmol/L. heart, blood vessels, and mushrooms. Ergocalciferol (D2)
rickets. Likely effective for In research, doses range from kidney), and increased risk for is suitable for vegetarians and
corticosteroid induced 400 IU to 50,000 IU/day. The kidney stones. Risk may be vegans.
osteoporosis, fall prevention tolerable upper limit (UL) is increased in postmenopausal
in older adults, osteoporosis. 4000 IU (100 mcg)/day. women who also take
Possibly effective for supplemental calcium. Best to
prevention of cancer, dental coordinate care with primary
caries, multiple sclerosis, care provider and monitor
respiratory tract infections, blood levels.
rheumatoid arthritis, and
obesity.
Vitamin E Effective for vitamin E deficiency. Most supplements are between Doses above 400 IU/day may D-alpha tocopherol is the natural
Possibly effective for 50 and 2000 IU. increase risk for bleeding, form of vitamin E and dl-alpha
slowing cognitive decline Most common dose is 200-400 prostate cancer, and have tocopherol is the synthetic form.
in Alzheimer’s disease, IU/day. prooxidant effects. Natural forms with mixed
improving response to tocopherols, specifically gamma
erythropoietin in tocopherol, may have
hemodialysis, reducing cardioprotective effects.
cisplatin induced neurotoxicity Supplemental Vitamin E has
and pain in rheumatoid been linked with prostate cancer
arthritis, prevention of in the SELECT trial. This result
dementia, dysmenorrhea, was not found in other studies
premenstrual syndrome (Physicians’ Health Study II [PHS
(PMS), Parkinson’s disease, II] and Women’s Health Study
and radiation induced fibrosis (WHS)).
and increasing muscle
strength in older adults.
Folic acid/Folate Effective for folate deficiency. Recommended dietary allowance Excess folic acid (5 mg and Supplemental sources have greater
Likely effective for (RDA) level is recommended in above) can cause B12 bioavailability than folate in
hyperhomocysteinemia, most people, although those deficiency. Folic acid food. People with a MTHFR
methotrexate toxicity, and with MTHFR variant or chronic supplements can also mask variant may have increased need
neural tube defects. Possibly conditions may need higher B12 deficiency. Caution with for folate. The methylated form,
effective for age-related levels (200 mcg-5 mg/day has folic acid supplementation in methylenetetrahydrofolate is
macular degeneration, been used although 800 mcg- those at risk for colon cancer. also used.
depression, hypertension. 1000 mg is most common).
Coordinate care with physician
for megadose amounts. The
Institute of Medicine (IOM)
recommends adults limit their
intake from supplements and
fortification to 1000 mg/d
Minerals
Calcium Effective for dyspepsia, 500-1000 mg/day is a typical High doses can increase risk for Chelated forms such as citrate and
hyperkalemia, and renal dose. kidney stones, cardiovascular malate are better absorbed than
failure (as a phosphate Do not exceed the UL. disease (CVD), and carbonate unless taken with a
binder). Likely effective for constipation. CVD risk is meal. Coadministration with
osteoporosis, corticosteroid greater in postmenopausal vitamin K may be helpful to
induced osteoporosis, women who take reduce risk of hypercalcemia
hyperparathyroidism, and supplemental calcium. except in those taking blood-
premenstrual syndrome. Caution in patients with thinning medications
Possibly effective for reducing hyperparathyroidism.
risk of colorectal cancer,
hypercholesterolemia,
hypertension, and prevention
of weight gain.
Continued
200 PART II Nutrition Diagnosis and Intervention

BOX 11.7 Popular Dietary Supplements and Their Efficacy—cont'd

Potential
Supplement Benefits Dosage Contraindications Quality Considerations
Chromium Effective for chromium Studies have used 150-1000 Trivalent chromium is found in Chromium picolinate is the most
deficiency. Possibly effective mcg/day. Adequate intakes appropriate dietary common form and is thought to
for reducing blood sugar in are thought to be 25-35 mcg/ supplements. Poor quality be well absorbed.
diabetes, decreasing low- day for adults. No UL has brands may contain
density lipoprotein (LDL) been established. hexavalent chromium, which
cholesterol, and triglycerides. is toxic and linked to cancer.
Caution in those with
diabetes, renal impairment.
Higher doses may cause
dermatitis and/or
gastrointestinal irritation.
Iron Effective for iron deficiency RDA is recommended unless Ensure the presence of iron Chelated iron (citrate, bisglycinate)
anemia and pregnancy blood work indicates deficiency anemia before and Feosol® (carbonyl iron) may
induced anemia. Possibly increased need. Needs supplementing with iron (also be better tolerated and cause
effective for ACE inhibitor increase in pregnancy. check ferritin level). Do not fewer gastrointestinal side
induced cough, cognitive Vegetarians may need higher exceed the UL except with effects.
function, restless leg levels because of decreased coordination of care with a
syndrome, and heart failure bioavailability from plant physician. Excessive iron
foods. 4-6 mg/kg/day or intake can cause nausea,
60-120 mg/day for those with constipation, and black stools
anemia. Some research and may increase the risk of
shows intermittent doses heart disease.
(several times a week to
weekly) can be effective
for prevention of anemia in
multiple populations.
Magnesium Effective for constipation, Typical dose is 100-500 mg/day. The most common side effects Chelated forms such as citrate,
dyspepsia, preeclampsia, and Exceeding the UL from with high doses are diarrhea, bisglycinate, and amino acid
eclampsia. Possibly effective for supplements (350 mg/day) is bloating, and reduction in chelate may be better absorbed
asthma prevention, cancer not recommended because of blood pressure. Serious side and tolerated (less GI side
associated neuropathic pain, potential for diarrhea. effects are a risk with IV effects) than oxide form.
chronic fatigue syndrome, magnesium, including
chronic obstructive pulmonary hypotension, nausea, and
disease (COPD), cluster ataxia.
headaches, osteoporosis,
diabetes (improved blood
glucose control), and vasospastic
angina. IV forms are effective for
cardiac arrhythmia, acute pre
term labor and acute asthma
attacks. Magnesium is often
used in fibromyalgia and
migraine headache, but the
results are mixed.
Selenium Possibly effective for Daily recommended intake is Gastrointestinal symptoms, Brazil nuts are an excellent source
autoimmune thyroiditis, 55-70 mcg/day although most nausea, and vomiting are of selenium. Selenium and
dyslipidemia, prevention of supplemental doses are in the most common with high vitamin E have a synergistic
HIV virus replication and 100-200 mcg range. doses. Acute toxicity may effect and are best taken
increased immune cell count, Exceeding the UL of 400 mcg/ impair liver, kidney, and together.
reduced risk of cancer and day is not recommended. cardiac function.
cancer mortality with good
selenium status. Used as an
antioxidant supplement as a
cofactor for selenocysteine
and glutathione production.
 CHAPTER 11 Food and Nutrient Delivery: Bioactive Substances and Integrative Care 201

BOX 11.7 Popular Dietary Supplements and Their Efficacy—cont'd

Potential
Supplement Benefits Dosage Contraindications Quality Considerations
Zinc Likely effective for diarrhea and Doses vary depending on Mostly nontoxic below the UL of Take zinc supplements with copper
Wilson’s disease. Possibly condition. 15-45 mg/day 40 mg/day in adults. High zinc to prevent depletion of copper.
effective for acne, age-related range is common. Much intake can deplete copper and Zinc lozenges have been used to
macular degeneration, higher doses sometimes given can cause nausea, dermatitis, prevent and treat the common
anemia, anorexia nervosa, for wound healing short term. and copper deficient anemia. cold.
attention deficit hyperactivity Coordination of care
disorder, burns, common cold, recommended.
dandruff, depression, diabetic
foot ulcers, diaper rash,
halitosis, gingivitis, herpes
simplex virus, muscle cramps,
radiation mucositis,
osteoporosis, peptic ulcers,
pressure ulcers, sickle cell
disease, vitamin A deficiency,
warts
Other Supplements
Arginine Possibly effective for angina, Therapeutic dose range is High doses may increase No special production or quality
erectile dysfunction, thought to be from bleeding in those on warfarin, control issues with arginine.
hypertension, necrotizing 400-6000 mg/day. There is no may lower blood sugar and L- arginine is the active form.
enterocolitis (NEC), peripheral tolerable upper limit and blood pressure. Caution in
artery disease, post-surgery higher doses (up to those with history of
recovery, and preeclampsia. 30 g/day) have been used. myocardial infarction or
Coordination of care cancer
recommended
Beta-glucans Likely effective for 3 g beta-glucan/day (from oats) Generally well tolerated with Found widely in plant-based foods,
hyperlipidemia. Possibly per the FDA as a cholesterol few side effects. especially oats and mushrooms.
effective for allergic rhinitis lowering food. In supplements, May cause mild gastrointestinal
(hay fever), cancer survival, 2-16 g/day is common dosing symptoms in some. Can lower
and postoperative infection. for hyperlipidemia. blood pressure and blood
Beta glucans can stimulate sugar
the immune response
including upregulating natural
killer cells and tumor necrosis
factor.
Coenzyme Q10 Possibly effective for mitochon- Doses vary from 30-600 mg/day. Very few side effects reported Oil-based preparations may be
(Ubiquinone) drial encephalomyopathies, The most common dosing is other than mild nausea, better absorbed. Ubiquinol is the
age-related macular degener- 100-200 mg/d in divided headache, and skin itching. active form and may be more
ation, cardiovascular mortal- doses May decrease blood pressure. biologically active, although
ity, congestive heart failure, Caution with people on blood- most people are able to convert
diabetic neuropathy, HIV/ thinning medications ubiquinone to ubiquinol without
AIDS, hypertension, ischemic problems.
reperfusion injury, migraine
headache, and Parkinson’s
disease.
Creatine Possibly effective for athletic Usually taken as a loading Considered safe for healthy Usually sold as creatine
performance enhancement dose of 20 grams per day people. monohydrate.
(muscle mass and muscle for 4-7 days followed by Increased fluid needs when
strength) and age-related a maintenance dose of taking creatine.
muscle loss. 2-10 grams per day for up Caution with kidney disease
to 14 weeks in conjunction especially if taking
with strength training. Doses nonsteroidal antiinflammatory
up to 30 g have been taken drugs (NSAIDs).
safely short term. Increased symptoms of anxiety
and depression have been
noted.
Continued
202 PART II Nutrition Diagnosis and Intervention

BOX 11.7 Popular Dietary Supplements and Their Efficacy—cont'd

Potential
Supplement Benefits Dosage Contraindications Quality Considerations
DHEA Possibly effective for aging skin Dose should be recommended May increase estrogen and 7 Keto dehydroepiandrosterone
Dehydroepiandros- and depression. Mixed results by a physician and based on testosterone and risk for (DHEA) is a metabolite of DHEA
terone in studies on use in adrenal laboratory results. Doses hormone imbalance and that is not converted into
insufficiency, depression, range from 5-450 mg/day. cancer. estrogen or testosterone and is
chronic fatigue syndrome, May increase acne, facial hair thought to be a safer alternative
fibromyalgia, HIV/AIDS, growth, and cause other to DHEA.
osteoporosis, physical hormonal side effects.
performance, sexual Avoid with hormone blockers
dysfunction, weight loss. such as tamoxifen. Multiple
Most doctors treat with contraindications.
DHEA based on individual
laboratory values.
Fish oil Effective for hypertriglyceride- 1-4 g/day of eicosapentaenoic More than 3 g/day EPA/DHA Molecular distilled fish oil is
mia. Likely effective for acid (EPA) and docosahexae- may increase risk for considered the best quality. For
cardiovascular disease. noic acid (DHA) combined. bleeding, bruising, and vegetarians, flaxseed oil may
Possibly effective prevention Up to 3 g/day is considered elevation in blood sugar. also be beneficial. Use cold
of restenosis after angioplasty generally recognized as safe Caution with people on blood- pressed oil in dark bottles or
and coronary artery bypass (GRAS) and the Food and Drug thinning medications and refrigerate. The International
grafts, attention deficit Administration (FDA) those with diabetes (may Fish Oil Standards (IFOS) website
hyperactivity disorder, bipolar recommends not exceeding 2 increase blood glucose above lists brands that have passed
disorder, cachexia, dysmenor- g/d EPA/DHA from dietary 3 grams EPA/DHA). strict international standards for
rhea, heart failure, hyperten- supplements. purity.
sion, psoriasis, Raynaud’s
syndrome, rheumatoid
arthritis, stroke. Conflicting
evidence for depression,
eczema, inflammatory
bowel disease, autism.
Glucosamine Possibly effective for mild to Typical dose for joint conditions Considered to be a safe Most research has been done on
moderate osteoarthritis; is 1500 mg/day taken in supplement for most glucosamine sulfate form,
conflicting or insufficient 2-3 divided doses. people. although glucosamine
evidence to rate effectiveness Lower doses of 400-1000 mg/day Most is sourced from shellfish, hydrochloride has also been used
for interstitial cystitis and have been used for other so may be an allergen in with success. Glucosamine is
temporomandibular (TMJ) conditions. some. often sold in combination with
disorders and postoperative High doses can disrupt chondroitin for added benefit.
recovery. blood sugar metabolism
in those with diabetes.
Caution in those with renal
dysfunction or in those
taking warfarin.
Glutamine Possibly effective for use in 5-30 g/day orally is a typical Considered safe. Many drugs Take separately from food
burn patients, bone marrow dose. deplete body stores of (especially protein) for maximal
transplants, burns, critical ill- Doses in IV or total parenteral glutamine. Caution with absorption.
ness (trauma), AIDS wasting, nutrition (TPN) in the critically higher doses in those with
and to improve nitrogen bal- ill may be higher. renal or liver impairment due
ance after surgery. Conflicting to nitrogen content.
evidence for use with diarrhea
(especially due to chemother-
apy), oral mucositis, inflam-
matory bowel disease and
short bowel syndrome.
 CHAPTER 11 Food and Nutrient Delivery: Bioactive Substances and Integrative Care 203

BOX 11.7 Popular Dietary Supplements and Their Efficacy—cont'd

Potential
Supplement Benefits Dosage Contraindications Quality Considerations
Melatonin Likely effective for delayed sleep 500 mcg-5 mg/day have been Generally regarded as safe for Usually taken 30 minutes before
phase syndrome and sleep used in research. 3-5 mg/day use up to 3 months and is bed for sleep disorders.
disorders, especially in the is the most common dose. even tolerated in neonates.
blind. Possibly effective for 10-40 mg has been used for Most common side effects are
insomnia, benzodiazepine tumor regression— headache, nausea, and
withdrawal, jet lag. High coordination of care with an drowsiness. May lower blood
doses have been used oncologist is essential. pressure and disrupt hormone
to promote tumor balance.
regression in some forms
of cancer.
Probiotics Likely effective for rotaviral Dosage varies and is measured May be contraindicated in the Refrigeration is important to
(lactobacillus diarrhea. Possibly effective for in colony forming units (CFUs). immune suppressed, those preserve quality in most
acidophilus and antibiotic associated diarrhea, Range is 1-450 billion CFU with central line placement products; however, some
bifidobacteria) atopic dermatitis (eczema), depending on the disease (especially saccharomyces products are shelf stable.
clostridium difficile diarrhea, condition and therapeutic boulardii), and in those on Yeast-based probiotics
chemotherapy induced goal. hemodialysis due to risk of (saccharomyces boulardii)
diarrhea, constipation, sepsis. are shelf stable.
Helicobacter pylori May cause diarrhea in high
inflammation, infantile colic, doses especially if the
irritable bowel syndrome, supplement contains
pouchitis, respiratory tract prebiotics like inulin.
infections, travelers diarrhea, May be contraindicated in
ulcerative colitis premature infants with risk of
bacteremia.
Herbs
Chamomile Possibly effective for anxiety, 250-1100 mg/day in capsules or GRAS. Caution in those with Ensure correct plant is used.
Matricaria recutita colic, diarrhea, dyspepsia, and 1-4 cups/day as tea. allergy to ragweed or German chamomile (not
(German Chamomile) oral mucositis. Asteraceae family. Roman Chamomile) is the
most common.
Cinnamon Possibly effective for reducing Typical dose is 120 mg-6 g/day Generally safe. Caution in people Cassia cinnamon is more
Cinnamomum fasting glucose in diabetes. in capsules or 1 tsp/day in with diabetes or blood sugar biologically active than Ceylon
cassia food. dysregulation or in those with cinnamon for blood sugar
impaired liver function. regulation.
May enhance blood-thinning
effects of warfarin.
Cranberry Possibly effective for urinary As juice: 1 oz cranberry Generally safe. Caution with Blueberries have similar
Vaccinium tract infection, (prevention concentrate or 10 oz cranberry sugar in juice for diabetics, constituents and may be
macrocarpon and treatment). Preliminary cocktail (sweetened). As may increase calcium oxalate similarly beneficial. Many
evidence for reducing urinary capsules: 300-500 mg kidney stones. supplements are standardized to
odor and improving symptoms twice/day or 200 mg contain a specific amount of
in benign prostatic twice/day with 25% PAC. This preparation may have
hyperplasia (BPH). standardization of a stronger effect.
proanthocyanidins
(PAC).
Echinacea Possibly effective for the Can be taken as a capsule, Caution in people with allergy to Sometimes standardized to contain
angustifolia, common cold. Insufficient tablet, tea, or tincture. Doses Asteraceae family (daisy, a specific amount of
pallida and evidence for influenza, herpes vary and are dependent on sunflower), and those on echinacoside or cichoric acid.
purpurea simplex virus, human the variety used and immunosuppressive
papilloma virus, and otitis preparation. medications.
media. 5 mL fresh juice or 20 drops in
water every 2 hours, 4 mL
10 times per day for the first
day of a cold then three times
a day for the duration.

Continued
204 PART II Nutrition Diagnosis and Intervention

BOX 11.7 Popular Dietary Supplements and Their Efficacy—cont'd

Potential
Supplement Benefits Dosage Contraindications Quality Considerations
Fenugreek Possibly effective for improving Highly variable. 5-100 grams of Long term studies lacking Ensure quality brand. In one case
Trigonella blood sugar control in ground seeds added to food although the seeds are a seeds were contaminated with E
foenum- diabetes and dysmenorrhea. although 2-5 grams 2-3 times staple some Asian cuisine. Coli and caused death. Generally
graecum Conflicting evidence for per day is most common. Therapeutic doses in children recognized as safe (GRAS) as a
promoting lactation, PCOS may be unsafe and not food.
and hyperlipidemia. recommended for use during
pregnancy (uterine stimulant).
Few side effects noted. More
than 100 grams may cause
hypoglycemia. Avoid use with
diabetes medications.
Garlic Possibly effective for 2-5 g fresh garlic, 0.4-1.2 g Generally well tolerated. Higher Comes in many forms in
Allium sativum atherosclerosis, reducing dried powder, 2-5 mg oil, doses may cause gastric supplements. Those that
blood sugar in diabetes, or 300-1000 mg extract to irritation, body odor, and preserve allicin content may be
reducing blood lipids in deliver 2-5 mg allicin (active decreased blood pressure. more effective. Aged extracts
hyperlipidemia, hypertension. constituent) per day. One Caution with those who are have shown benefits as well
Conflicting evidence for the clove fresh garlic has also taking blood thinners and because of the multitude of
common cold and cancer been used. hypoglycemic drugs. sulfur compounds present.
prevention.
Green tea Likely effective for Epigallocatechin (EGCG) epicate- Well tolerated in most people. Decaffeinated versions are
Camellia hyperlipidemia. Possibly chin gallate, and epicatechin Most side effects come from available to eliminate caffeine
sinensis effective for coronary artery levels vary when taken as tea. the caffeine content side effects.
disease, hypotension, 3 cups daily is a common (nervousness, anxiety,
Parkinson’s disease. dosage. Standardized extracts sleeplessness, and increased
Conflicting evidence for (60%-97% polyphenols) of blood pressure). Use with
cancer prevention, 200-500 mg/day are common caution in patients with
cardiovascular disease, for a variety of conditions. psychiatric or cardiovascular
and for weight loss. 10% topical cream for skin conditions.
aging and acne.
Kava Kava Possibly effective for anxiety; 60-400 mg standardized extract Typical therapeutic doses are Often standardized to contain
Piper insufficient evidence for per day. tolerated by most. Significant 30%-70% kavalactones. May
methysticum benzodiazepine withdrawal, evidence of liver injury. be best to start at lower doses
stress reduction, insomnia, Caution in people with liver and titrate up.
and menopausal anxiety. disease. Chronic use can
cause dry, scaly skin and
photosensitivity.
Milk thistle Although it is commonly used to 160-1200 mg/day based on Low toxicity risk. Can cause a Often standardized to contain
Silybum reduce inflammation and condition treated. Take as mild laxative effect if taken in 70%-80% silymarin. Tea
marianum fibrosis in liver disease, it is divided doses. 140 mg large amounts. Rare risk of preparation is not recommended
possibly effective for lowering standardized extract taken allergic reaction. May lower because of poor water solubility.
fasting glucose in diabetes, three times per day is a blood sugar. May mildly Whole, ground milk thistle seeds
and for dyspepsia. There is common dose. inhibit CYP 34A, 2C19, and can be added to food.
conflicting and insufficient 2D6 cytochrome enzymes.
evidence for alcohol related
liver disease, amanita
mushroom poisoning,
cirrhosis, and hepatitis
induced liver damage.
Red Yeast Likely effective for The most common dose is Limited data on adverse events. Contains naturally occurring
Rice (RYR) hyperlipidemia. Possibly 600- 2400 mg/day. It is Side effects appear to be lovastatin (Monacolin K). Dosing
Monascus effective for CVD and estimated that average similar to those with low-dose is difficult because of natural
purpureus diabetes and HIV/AIDS intake of naturally occurring statin medications (headache, variations in products. It is
related dyslipidemia. RYR in Asia is 14-55 g/day. gastrointestinal discomfort, illegal in the United States to
Preliminary evidence for and muscle pain). May standardize Monacolin K levels
use in nonalcoholic fatty increase liver enzymes. in supplements.
liver disease (NAFLD).
 CHAPTER 11 Food and Nutrient Delivery: Bioactive Substances and Integrative Care 205

BOX 11.7 Popular Dietary Supplements and Their Efficacy—cont'd

Potential
Supplement Benefits Dosage Contraindications Quality Considerations
St. John’s Wort Likely effective for mild to Typical dose is 300-450 mg three Has the most drug nutrient Typically standardized at 0.3%
Hypericum moderate depression. Possibly times per day. Coordination of interactions of any hypericin.
perforatum effective for menopausal care with a physician is common herb. Inhibits
symptoms, somatization important. CYP 34A, 2C19, and 2C9
disorder. Conflicting or cytochrome enzymes and
insufficient evidence for the P-glycoprotein (P-gp)
anxiety, obsessive compulsive transporter. Reduces the
disorder, premenstrual effectiveness of
syndrome, seasonal affective immunosuppressive,
disorder. Can be used antiretroviral, cardiovascular,
topically for wound healing. and oral contraceptive
medications among others.
Can cause photosensitivity.
Turmeric Possibly effective for allergic 500 mg-2 g curcumin per day Safe in amounts eaten in food. May be best absorbed when
Curcuma rhinitis, depression, depending on disease Higher doses can lower blood taken with food, especially
longa hyperlipidemia, NAFLD, condition. Higher doses pressure and blood sugar and a meal that contains fat.
ulcerative colitis, and taken in divided doses. increase risk of bleeding. Curcumin supplements bound
osteoarthritis. Conflicting Caution in those with liver to phosphatidyl choline (Meriva)
evidence for Alzheimer’s and gall bladder diseases and may be better absorbed.
disease, colorectal cancer, in those taking blood-thinning
Crohn’s disease, irritable medications.
bowel syndrome, rheumatoid
arthritis, and ulcerative colitis.
Natural Medicines Comprehensive Database. [Link]
Linus Pauling Institute. [Link]
Consumer Lab. [Link]

CLINICAL CASE STUDY

Ellen is a 60-year-old white female who was referred from her primary care Lunch: Frozen entrée—beef and broccoli with rice and a Diet Coke
provider for evaluation of her dietary supplements. Medical history includes hy- Snack: Strawberry yogurt and pretzels, coffee with milk
pertension, hypercholesterolemia, osteopenia, mild depression, and memory Dinner: Meatloaf, mashed potatoes with gravy and carrots. Glass of red wine.
problems. Two years ago, she had angioplasty (PTCA) with a stent placement in Dessert: Chocolate ice cream, coffee with milk
her coronary artery. Ellen is a retired school teacher, married, and has two grown
Nutrition Diagnostic Statements
children. Her neighbor works in a supplement store and recommended some
• Predicted food medication interaction (NC-2.4) related to a food and nutrition
herbs and supplements to address Ellen’s health concerns.
knowledge deficit about DNI's as evidenced by taking St. John's Wort with
At the initial consult Ellen reports she is taking the following supplements:
sertraline and the potential for serotonin syndrome.
calcium carbonate 1200 mg/d, garlic (Allium sativum) 500 mg/d, Ginkgo
• Altered nutrition related laboratory value (NC-2.2) related to knowledge defi-
biloba 240 mg/d, and St. John’s wort (Hypericum perforatum) 900 mg/d. Her
cit about DNI's, as evidenced by taking ginkgo and garlic with warfarin and
prescription medications include warfarin, simvastatin, sertraline, and
inconsistent INRs
atenolol.
Height: 640 Weight: 165 lbs BMI: 28.4 Nutrition Care Questions
Blood pressure readings: 134/92, 140/95 “This is higher than it usually is” Ellen 1. Using the Office of Dietary Supplements Fact Sheets (ODS website), identify
reports. what each dietary supplement Ellen is taking is used for and if it has good
Recent labs: evidence to support use.
Total cholesterol: 284 mg/dL 2. List any potential drug nutrient interactions (DNIs) Ellen may have with
High-density lipoprotein (HDL): 36 mg/dL her current concomitant use of medications and dietary supplements.
Low-density lipoprotein (LDL): 140 mg/dL 3. Looking at Ellen’s lab tests, is there any evidence she may be having a DNI?
Prothrombin times (INR) has been inconsistent lately. 4. Does Ellen need to be taking a calcium supplement? Are there any potential
Typical dietary intake includes the following: risks with taking 1200 mg/day with a positive history of cardiovascular
Breakfast: Total cereal with milk and calcium fortified orange juice disease (CVD)?
206 PART II Nutrition Diagnosis and Intervention

USEFUL WEBSITES Blumberg JB, Frei BB, Fulgoni VL, et al: Impact of frequency of multi-
vitamin/multi-mineral supplement intake on nutritional adequacy and
Free Sites nutrient deficiencies in U.S. adults, Nutrients 9:849–864, 2017.
Boden WE, Sidhu MS, Toth PP: The therapeutic role of niacin in dyslipidemia
FDA MedWatch
management, J Cardiovasc Pharmacol Ther 19(2):141–158, 2014.
Linus Pauling Micronutrient Information Center Bowman SA, Clemens JC, Friday JE, et al: Food patterns equivalents intakes by
Medscape Drug Interaction Checker Americans: what we eat in America, NHANES 2003-2004 and 2015-2016.
National Center for Complementary and Integrative Health Food Surveys Research Group. Dietary Data Brief No. 20, November 2018.
Natural Products Association Brown AC: An overview of herb and dietary supplement efficacy, safety and
Office of Dietary Supplements government regulations in the United States with suggested improve-
Operation Supplement Safety (U.S. Department of Defense) ments. Part 1 of 5 series, Food Chem Toxicol 107:449–471, 2017.
Chermesh I, Tamir A, Suissa A, et al: Ferrus calcium citrate is absorbed better
Subscription Sites than iron bisglycinate in patients with Crohn’s disease, but not in healthy
Cochrane Database Review controls, Dig Dis Sci 51(5):942–945, 2006.
Chew EY, Clemons TE, Agrón E, et al: Long-term effects of vitamins C and E,
Consumer Lab
b-carotene, and zinc on age-related macular degeneration: AREDS report
Dietitians in Integrative and Functional Medicine (DIFM) practice no. 35, Ophthalmology 120(8):1604–1611.e4, 2013.
group through the Academy of Nutrition and Dietetics Cohen PA, Maller G, DeSouza R, et al: Presence of banned drugs and dietary
Institute for Functional Medicine supplements following FDA recalls. JAMA 312(16):1691–1693, 2014.
Natural Medicines Database Council for Responsible Nutrition: 2017 CRN Consumer survey on dietary
supplements, 2017. Available at: [Link]
Text/Print consumer-survey-dietary-supplements.
Moyad M. The Supplement Handbook, New York, 2014, Rodale. Drake VJ and Frei B: Micronutrient inadequacies in the US population: an
overview, 2018. Available at: [Link]
Resources for Herbal Medicine inadequacies/overview#references.
Falci L, Shi Z, Greenlee H: Multiple chronic conditions and use of comple-
American Botanical Council (ABC)
mentary and alternative medicine among US adults: results from the 2012
American Herbal Products Association (AHPA) National Health Interview Survey, Prev Chronic Dis 13:E61, 2016.
American Herbalists Guild (AHG) Food and Drug Administration: Guidance for industry: current good manufac-
Dr. Duke’s Phytochemical and Ethnobotanical Database turing practice in manufacturing, packaging, labeling, or holding operations
for dietary supplements; small entity compliance guide, 2010. Available at:
[Link]
ryinformation/dietarysupplements/[Link].
Food and Drug Administration: Reports received and reports entered into
REFERENCES FAERS by year, 2012. Available at: [Link]
ComplianceRegulatoryInformation/Surveillance/AdverseDrugEffects/
Academic Consortium for Integrative Medicine and Health: Introduction, [Link].
2018. Available at: [Link] Food and Drug Administration: Guidance for industry: questions and answers
Academy of Nutrition and Dietetics: Position of the Academy of Nutrition regarding adverse event reporting and recordkeeping for dietary supplements
and Dietetics: micronutrient supplementation, J Acad Nut Diet as required by the dietary supplement and Nonprescription Drug Consumer
118(11):2162–2173, 2018. Protection Act, 2013. Available at: [Link]
American College of Surgeons, College of Education: Medication and information/search-fda-guidance-documents/guidance-industry-
surgery before your operation, 2014. Available at: [Link] questions-and-answers-regarding-labeling-dietary-supplements-
patienteducation/[Link]. required-dietary.
American Herbalists Guild: Herbal medicine fundamentals, 2019. Available at: Food and Drug Administration: Q and A on dietary supplements: what is a
[Link] dietary supplement? 2015. Available at: [Link]
Ames BN, Elson-Schwab I, Silver EA: High dose vitamin therapy stimulates DietarySupplements/QADietarySupplements/[Link]#what_is.
variant enzymes with decreased coenzyme binding affinity (increased Food and Drug Administration: Tainted products marketed as dietary supple-
K(m)): relevance to genetic disease and polymorphisms, Am J Clin Nutr ments potentially dangerous, 2018. Available at: [Link]
75:616–658, 2002. gov/scripts/sda/[Link]?sd5tainted_supplements_cder.
Augustine MB, Swift KM, Harris SR, et al: Integrative medicine: Education, Fortmann SP, Burda BU, Senger CA, et al: Vitamin, mineral and multivitamin
Perceived knowledge, attitudes and practice among Academy of Nutrition supplements for the primary prevention of cardiovascular disease and cancer:
and Dietetics Members, J Acad Nutr Diet 116(2):319–329, 2016. a systematic evidence review for the U.S. preventive services task force,
Bailey RL, Fakhouri TH, Park Y, et al: Multivitamin-mineral use is associated Report No.: 14-05199-EF-1. Rockville, MD, 2013, Agency for Healthcare
with reduced risk of cardiovascular disease mortality among women in the Research and Quality.
United States, J Nutr 145:572–578, 2015. Gahche J, Bailey R, Burt V, et al: Centers for disease control and prevention.
Bailey RL, Fulgoni VL III, Keast DR, et al: Do dietary supplements improve Dietary supplement use among US adults and children has increased since
micronutrient sufficiency in children and adolescents? J Pediatr 161: NHANESIII 2014. Available at: [Link]
837–842, 2012. [Link].
Bailey RL, Gahche JJ, Miller PE, et al: Why US adults use dietary supplements, Geller AI, Shehab N, Weidle NJ, et al: Emergency department visits for adverse
JAMA Intern Med 173(5):355–361, 2013. events related to dietary supplements, N Engl J Med 373(16):1531–1540,
Bjelakovic G, Nikolova D, Gluud LL, et al: Antioxidant supplements for 2015.
prevention of mortality in healthy participants and patients with various Gaziano JM, Sesso HD, Christen WG, et al: Multivitamins in the Prevention of
diseases, Cochrane Database Syst Rev 3:CD007176, 2012. Cancer in Men: The Physicians’ Health Study II Randomized Controlled
doi:10.1002/14651858.CD007176.pub2. Trial. JAMA 308(18):1871–1880, 2012.
Blumberg JB, Bailey RL, Sesso HD, et al: The evolving role of multivitamin/ Government Accountability Office: Dietary supplements: FDA may have
multi-mineral supplement use among adults in the age of personalized opportunities to expand its use of reported health problems to oversee
nutrition, Nutrients 10:E248–E265, 2018. products, 2013. Available at: [Link]
 CHAPTER 11 Food and Nutrient Delivery: Bioactive Substances and Integrative Care 207

Gurley BJ: Pharmacokinetic herb-drug interactions (Part 1): origins, National Institutes of Health: Dietary supplement Health and Education Act of
mechanisms, and the impact of botanical dietary supplements, Planta 1994 Public law 103-417 103rd Congress, 1994. Available at: [Link]
Med 78:1478–1489, 2012. [Link]/About/DSHEA_Wording.aspx.
Gurley BJ, Fifer EK, Gardner Z: Pharmacokinetic herb-drug interactions Noland and Raj: Academy of Nutrition and Dietetics: Revised 2019 Standards
(Part 2): drug interactions involving popular botanical dietary supple- of Practice and Standards of Professional Performance for Registered
ments and their clinical relevance, Planta Med 78:1490–1514, 2012. Dietitian Nutritionists (Competent, Proficient, and Expert) in Nutrition
Harris PE, Cooper KL, Relton C, et al: Prevalence of complementary and in Integrative and Functional Medicine. Jour of the Acad of Nut and Diet
alternative medicine (CAM) use by the general population: a systematic 119(6):1019–1036.e47, 2019
review, Int J Clin Prac 66(10):924–939, 2012. Obeid R, Fedosov SN, Nexo E, et al: Cobalamin coenzyme forms are not likely
Head KA: Peripheral neuropathy: pathogenic mechanisms and alternative to be superior to cyano- and hydroxyl-cobalamin in prevention or
therapies, Altern Med Rev 11(14):294–329, 2006. treatment of cobalamin deficiency, Mol Nutr Food Res 59(7):
Hendren RL: Autism: biomedical complementary treatment approaches, 1364–1372, 2015.
Child Adolesc Psychiatr Clin N Am 22:443–456, 2013. Peh HY, Tan WS, Liao W, et al: Vitamin E therapy beyond cancer: tocopherol
Horrigan B, Lewis S, Abrams D, et al: Integrative medicine in America. vs. tocotrienol, Pharmacol Ther 162:152–169, 2016.
How integrative medicine is being practiced in clinical centers across the Peregoy JA, Clarke TC, Jones LI, et al: Regional variation in use of
United States, 2012, The Bravewell Collaborative. Available at: [Link] complementary health approaches by US adults, NCHS Data Brief
[Link]/current_projects/mapping_field/. (146):1–8, 2014.
Institute for Functional Medicine: What is functional medicine? 2018. Quato DM, Alexander GC, Guadamuz JS, et al: Prevalence of dietary
Available at: [Link] supplement use in US children and adolescents, 2003-2014, JAMA Pediatr
Landvik S: Vitamin E from supplements has good bioavailability, Am J Clin 172(8):780–782, 2018.
Nutr 80(3):784–785, 2004. Rautiainen S, Rist PM, Glynn R, et al: Multivitamin use and the risk of
Long J: FDA still finding same cGMP deficiencies at dietary supplement facilities, cardiovascular disease in men, J Nutr 146:1235–1240, 2016.
2018, Natural Products Insider. Available at: [Link] Smith T, Kawa K, Eckl V, et al: Herbal Supplement Sales in US
[Link]/regulatory/fda-still-finding-same-cgmp-deficiencies- Increased 8.5% in 2017, Topping $8 Billion, Herbal Gram 119:62–71,
dietary-supplement-facilities. 2018.
Morton C: State of the supplements industry. Nutrition business journal Straub DA: Calcium supplementation in clinical practice: a review of forms,
(Data brief online), 2018. Available at: [Link] doses, and indications, Nutr Clin Pract 22(3):286–296, 2007.
[Link]/files/[Link]. Thompson C, Diekman C, Fragakis AS, et al: Guidelines regarding the
National Center for Complementary and Integrative Health: Complementary, recommendation and sale of dietary supplements, J Am Diet Assoc
alternative, or integrative health: what’s in a name? 2018. Available at: 102(8):1158–1164, 2002.
[Link]