Dietary Supplements for APRNs Part 3: Botanicals/Herbals, Amino Acids, Probiotics, and Fish Oil Nursing CE Course

1.5 ANCC Contact Hours 1.5 ANCC Pharmacology Contact Hour(s)

Disclosure Form

The purpose of this module is to provide an overview of the various dietary supplements with a focus on botanicals, herbals, amino acids, and probiotics including the potential benefits, risks, and impacts for patients utilizing these products.

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

  1. Consider the implications of the use of herbal supplements.
  2. Describe the benefits of amino-based dietary supplements.
  3. Explore the therapeutic use of probiotic supplements.
  4. Discuss the potential benefits of fish oil supplements.


Terms

Amino acids are the building blocks of life, a class of organic compounds that combine to form proteins (The National Library of Medicine [NLM], 2020a).  

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

Botanicals/Herbs

A botanical is a plant or a plant portion that is used for its therapeutic or medicinal properties, flavors, or scents. Herbs are a type of botanical.  Products that are made from botanicals to maintain or improve health are called botanical products, herbal products, or phytomedicines. Botanicals may be sold as fresh or dried products, liquid or solid extracts, tablets, capsules, powders, or teas. Typically, dietary supplements are dispensed in tablet or capsule forms. Botanicals may have specific chemicals known as markers that are used to manufacture a consistent or standardized product; this should be the portion of the botanical that provides the therapeutic effect. It is difficult to determine the quality of a botanical dietary supplement from its label as the quality is related to the manufacturer, supplier, and production process. Many people take botanicals and herbs for various conditions because they are natural substances, but the validity of their usefulness is primarily unsubstantiated by research. Many of these dietary supplements can be harmful, causing serious adverse effects. Those at highest risk for these effects are pregnant women and those who take anticoagulation therapy or have bleeding problems. This education module will serve as a review of specific herbs and their clinical considerations (The National Institutes of Health [NIH], 2011). 

Black Cohosh

Black cohosh is a member of the buttercup family and is native to North America. This herb has been used for centuries and has had many different names including snakeroot and black bugbane. Native Americans use black cohosh as a treatment for respiratory symptoms (including pneumonia), musculoskeletal pain, menstrual problems, and fever. Settlers from Europe used the herb to improve women’s reproductive health. Contemporary use of black cohosh is primarily to treat menopausal symptoms, particularly hot flashes and night sweats, as well as vaginal dryness, vertigo, sleep problems, irritability, and heart palpitations. Black cohosh supplements are made from the roots and underground stems (rhizomes); they are sold in powdered whole herb, liquid extracts, and dried pill forms. Remifemin is a commercially available black cohosh product that has been studied for efficacy in menopausal symptoms. Doses range from 6.5 to 160 mg/d, with a median dose of 40 mg/d. While there is a low incidence of side effects with black cohosh, there have been reports of liver damage with high doses or extended use. It is suggested that the use of black cohosh be limited to six months or less (NIH, 2018). Black cohosh is not advised in patients with estrogen-receptor positive cancers (i.e. breast), patients on tamoxifen (due to insufficient data in the literature), and also causes synergistic effects when taken with statin (lipid-lowering) medications (Memorial Sloan Kettering Cancer Center, 2020).

Echinacea

There are nine species of echinacea and all are native to North America. They were formerly used by Native Americans of the Great Plains region as traditional medicines. Echinacea is promoted as a dietary supplement for the prevention or treatment of infections such as the common cold. Topical echinacea preparations are applied to the skin for wounds or other skin conditions. Echinacea is made from the roots and above-the-ground portion of the echinacea plant in the form of teas, juice, extracts, capsules, tablets, or preparations for external use. Research regarding echinacea and the common cold indicate that there is no proven benefit once a person has a cold (treatment), but that it may reduce the risk of contracting a cold slightly (prevention). It is thought that echinacea may boost the human immune system and research is ongoing. Short term use of the herb appears safe, but long-term use is questionable. Common adverse effects are nausea or stomach pain and allergic reactions are possible. The risk of interactions between echinacea and other drugs is low (National Center for Complementary and Integrative Health [NCCIH], 2016a).

Garlic

Garlic is an edible bulb from the lily family and has traditionally been used around the world for health purposes. Today, fresh, powdered, or garlic oil is used to flavor foods. Garlic oil can also be applied topically for skin conditions. Garlic dietary supplements can be used for lowering blood pressure or cholesterol and prevention and/or treatment of the common cold. Other claims for garlic include preventing stomach and colon cancers. The National Cancer Institute recognizes garlic as a vegetable that has potential anticancer properties but does not advocate for taking a garlic supplement to prevent cancer. The evidence is weak for most health claims related to garlic, yet it is considered safe in the amounts that are typically ingested in foods or taken in supplements. Garlic may interact with blood thinners such as warfarin (Coumadin) and antiviral drugs such as saquinavir (Invirase) and ritonavir (Norvir), so patients on these medications should be counseled to avoid this particular supplement (NCCIH, 2016b). 

Ginkgo Biloba

Ginkgo is one of the oldest living tree species in the world and was originally used in traditional Chinese medicine. Historically, ginkgo biloba has been used for asthma, bronchitis, and urinary disorders. Supplements today are promoted for dementia, intermittent claudication (leg pain caused by narrowed arteries and insufficient blood flow), eye problems, and tinnitus. Ginkgo biloba is available in tablets, capsules, teas, extracts, and cosmetics. There is no solid research that ginkgo biloba improves any health conditions. In a study of more than 3,000 older adults, there was no evidence that ginkgo biloba slowed or prevented dementia or cognitive decline in the treatment group. It does appear to be safe when taken in moderate amounts. It increases the risk of bleeding and should be used with caution in patients taking anticoagulants such as warfarin (Coumadin). In a 2013 study lasting two years, rodents given ginkgo biloba had an increased risk of liver and thyroid cancer. Ingesting raw or roasted ginkgo seeds can have serious adverse effects and is considered poisonous (NCCIH, 2016c). 

Saw Palmetto

Saw palmetto is a small palm tree that grows in the southeastern US and was used medicinally by the Seminole Tribe. Saw palmetto is promoted as a dietary supplement for the management of urinary problems associated with an enlarged prostate, chronic pelvic pain, migraines, hair loss, or a decreased sex drive. Extracts of the fruit of the saw palmetto can be ground into powder, dried, whole berries, used in tablets, capsules, liquid extract, or teas. Several high-quality studies have determined that saw palmetto is no more effective than a placebo in relieving urinary symptoms associated with an enlarged prostate, including doses up to three times what is typical. Saw palmetto is tolerated with minimal side effects and does not interact with other medications (NCCIH, 2016d). 

St. John’s Wort

St. John’s wort is a plant that has been used in traditional medicine going back to ancient Greece. It is a small yellow flower that blooms around the feast of John the Baptist in late June, providing the inspiration for its name. The tops of the plant are used to prepare tablets, capsules, liquid extracts, or teas. This herb has been used for depression, kidney and lung ailments, insomnia, and as an aid for wound healing. Today it is primarily used for depression and occasionally for menopausal symptoms, ADHD, irritable bowel syndrome (IBS), or obsessive-compulsive disorder (OCD). It is used topically for wound healing as well. Several large studies have been completed to determine its effectiveness and interactions with other medications, revealing several life-threatening interactions and mixed data about its effectiveness. St John’s wort appears effective in depression but is ineffective as a treatment for ADHD or IBS.  Furthermore, the evidence is inconclusive regarding menopausal symptoms, premenstrual syndrome, or OCD (NCCIH, 2016e). 

St. John’s wort can decrease the effects of several medications including:

  • HIV drugs such as indinavir (Crixivan),
  • Cancer medications such as irinotecan HCL (Camptosar),
  • Antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs),
  • Cyclosporine (Neoral),
  • Digoxin (Lanoxin),
  • Birth control pills, or 
  • Warfarin (Coumadin) (NCCIH, 2016e). 

Adverse effects include sunlight sensitivity, anxiety, dizziness, GI symptoms, sexual dysfunction, dry mouth, or headache. Since depression is a serious illness, the individual taking St. John’s wort should be monitored closely for increasing depression or suicidal ideations (NCCIH, 2016e). 

Amino Acids

Amino acids play a vital role in body processes such as the synthesis of hormones and neurotransmitters and the building of proteins. They are referred to as the "building blocks of proteins." Amino acids are naturally occurring in foods but can also be taken as dietary supplements to enhance mood or athletic performance; they are categorized as essential, nonessential, or conditionally essential (Kubala, 2018). 

Amino acids are made up of carbon, nitrogen, hydrogen, and oxygen, as well as a variable side chain group. The body needs 20 specific amino acids for proper growth and development, but nine of these are considered essential (histidine, leucine, methionine, threonine, valine, L-tryptophan, isoleucine, lysine, and phenylalanine). These are considered essential because the body is unable to produce them endogenously and it depends entirely on dietary intake. Optimal sources for amino acids are animal proteins, including meat, eggs, and poultry. Proteins are broken down into amino acids for use by the body. Nonessential amino acids include those produced endogenously by the body (alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, proline, glycine, serine, and tyrosine). Conditionally essential amino acids are those that become essential under special circumstances such as stress or illness (i.e., cancer, wound healing, liver disease, premature infants). The conditionally essential amino acids are glutamine, cysteine, tyrosine, and ß-hydroxy ß-methylbutyrate (HMB) (NLM, 2020a). 

Essential Amino Acids

Phenylalanine

Phenylalanine plays a vital role in the structure and function of proteins and enzymes and is a precursor for the neurotransmitters dopamine, epinephrine, norepinephrine, and tyrosine. In addition to meats, eggs, and dairy, phenylalanine is also found in artificial sweeteners that contain aspartame. Phenylalanine at sufficiently high levels can act as a neurotoxin, disrupting or attacking neural tissue, or a metabotoxin, an internally produced metabolite that causes severe adverse effects at continuously high levels (NLM, n.d.). 

Valine

Valine helps stimulate muscle growth and regeneration. It is also involved in energy production. It is a branched-chain amino acid (BCAA) that has no significant use as an individual supplement. It is considered to be the least important BCAA for body composition (Patel, 2019). 

Threonine

Threonine is used for muscle control disorders marked by muscle tightness and involuntary movements such as MS, Lou Gehrig's disease, or other inherited disorders marked by leg stiffness or weakness. After ingesting, threonine becomes glycine, which works in the brain to decrease constant or unwanted muscle contractions. The typical dose is 1.5 to 2 g TID (three times per day) with inherited disorders, 2.5 g TID in MS, and 2 to 4 g daily with Lou Gehrig's disease (WebMD, n.d.g).

L-Tryptophan

L-tryptophan is required for serotonin production, which is a primary regulator of mood, behavior, and sleep. Low serotonin levels are linked to depression and sleep disorders. Several studies have linked supplementation of L-tryptophan with a reduction in depression symptoms, including improved sleep and improved mood. One of the many studies including women 60 years or older found a significant improvement in energy and happiness with 1 g of L-tryptophan supplementation in comparison to placebo (Jenkins et al., 2016). L-tryptophan has also been somewhat effective for smoking cessation and the treatment of teeth grinding and myofascial pain syndrome, a condition with persistent muscle pain (WebMD, n.d.c). 

Methionine

Methionine is most often taken to treat liver disorders and viral infections, even though little research exists regarding its efficacy. It is also used with acetaminophen (Tylenol) overdose treatment to prevent the byproducts from damaging the liver. Treatment should begin within ten hours of ingesting acetaminophen (Tylenol). Other uses of methionine are to reduce the risk of breast cancer, colon cancer, neural tube defects, and hot flashes. Early research suggests that taking methionine orally for up to six months can improve the symptoms of Parkinson's disease, such as tremor and rigidity. Methionine is suggested in treating herpes simplex virus (HSV), shingles, human papillomavirus (HPV), pancreatitis, depression, alcohol use disorder, allergies, asthma, radiation side effects, schizophrenia, drug withdrawal, or urinary tract infections (UTIs) with no evidence to support its effectiveness (WebMD, n.d.d). 

Leucine

Leucine is another BCAA that is crucial in muscle repair and protein synthesis. Leucine helps to regulate blood glucose levels, produce growth hormones, and stimulate wound healing. In a Japanese study, participants taking 2 g of leucine alone had higher concentrations of leucine after exercise than those gaining their leucine from a meal high in the amino acid. However, there were no significant benefits noted otherwise (Menayang, 2018). 

Isoleucine

Isoleucine is the third BCAA and is able to induce muscle protein synthesis at a moderate level, more than valine but less than leucine. It increases glucose uptake and usage during exercise, making it useful as a performance enhancer by athletes. Isoleucine is also important for immune function, energy regulation, and hemoglobin production (Kubala, 2018). 

Lysine

Lysine is involved in protein synthesis, hormone production, enzyme production, and the absorption of calcium. Lysine is further noted for energy production, immune function, as well as collagen and elastin production (Kubala, 2018). 

Histidine

Histidine is used for metabolic syndrome, diarrhea related to cholera infection, rheumatoid arthritis (RA), gastric ulcers, anemia associated with kidney failure, and allergic conditions. However, histidine’s effectiveness in the treatment of anemia associated with kidney failure/dialysis and RA has not been scientifically proven. Insufficient evidence exists for its use with cholera, although diarrhea was reduced in severity and duration with use. Similar results exist for metabolic syndrome, as early research shows that histidine administration for 12 weeks or more decreases body mass index and insulin resistance in obese women with metabolic syndrome (WebMD, n.d.b).

Select Nonessential and Conditionally Essential Amino Acids

While all amino acids will not be discussed in this module, several of the more common ones used by athletes or for specific conditions are listed below. For further information on various amino acids found in dietary supplements, a complete listing can be found in the US National Library of Medicine-Herbs and Supplements (NLM, 2020a).

Branched-Chain Amino Acids (BCAAs)

Three of the essential amino acids, leucine, isoleucine, and valine, are BCAAs. BCAAs are primarily found in eggs, meat, and dairy products. There are five proven benefits of BCAA supplements: increased muscle growth, decreased muscle soreness, reduction in exercise fatigue, prevention of muscle wasting, and improvement in liver disease such as cirrhosis. Research has provided evidence of these benefits, such as a study that followed people drinking 5.6 g of BCAAs after their resistance workout which lead to a 22% increase in muscle protein synthesis in comparison to the placebo group. A similar study assessed people that drank a BCAA supplement before a squat exercise who report reduced muscle fatigue and delayed onset muscle soreness (DOMS) in comparison to the placebo group. Other studies have shown that mental focus during exercise improves when taking BCAAs in comparison to a placebo, and muscle protein breakdown is inhibited with the use of BCAA supplements among the elderly and those with cancer at high risk for muscle wasting (Van de Walle, 2018a). 

Glutamine

Glutamine plays a critical role in the immune system and intestinal health. While the body produces glutamine naturally, supplements may be needed in some instances. Glutamine comes in two forms, L-glutamine and D-glutamine. The form found in foods and supplements is L-glutamine. Studies have shown that glutamine supplementation can decrease infection, improve overall health, and lead to shorter hospitalizations in comparison to placebo. High-glutamine diets or glutamine supplements are often utilized for patients with significant burn injuries or serious infections. Other studies have demonstrated that there is minimal difference in the muscle mass of bodybuilders using a glutamine supplement versus placebo. However, there are reports of decreased fatigue and muscle soreness during and after exercise (Tinsley, 2018).

Aspartate

Aspartate supplements are often called aspartic acid and typically combined with minerals such as copper aspartate, iron aspartate, magnesium aspartate, or zinc aspartate. Aspartate increases the absorption of minerals they are combined with and are believed to enhance athletic performance. Some forms are used to slow brain damage caused by cirrhosis of the liver and given intravenously in the healthcare setting. Currently, there is insufficient evidence to assess its effectiveness for any of these indications (RxList, n.d.). 

Arginine

Arginine, or specifically L-arginine, is often used after surgery and for the treatment of preeclampsia (hypertension during pregnancy in combination with protein in the urine), cardiovascular conditions (hypertension), angina (chest pain), peripheral arterial disease, and erectile dysfunction. There is insufficient data to assess its effectiveness for any of these uses. Studies indicate a decrease in chest pain and an improvement in exercise tolerance for individuals suffering from angina. L-arginine may interact with antihypertensive drugs such as captopril (Capoten), enalapril (Vasotec), or diltiazem (Cardizem). Sildenafil (Viagra) interacts with L-arginine and may cause hypotension. L-arginine in combination with nitroglycerin (Nitro-Bid, Nitro-Dur, or Nitrostat) or isosorbide (Imdur, Isordil) can cause dizziness and lightheadedness (WebMD, n.d.a).

Ornithine

Ornithine is commonly used to enhance athletic performance, weight loss, wound healing, or to improve sleep quality. There is limited scientific evidence to support these indications, however. When used for athletic performance, it is thought to reduce fatigue and improve speed, strength, or power in some individuals. Taking ornithine in combination with L-arginine is a common practice to improve strength and power in male weightlifters. There are no specific adverse effects or drug interactions to be aware of (WebMD, 2020e).

Tyrosine

Tyrosine is used for improved alertness, attention, or focus. Tyrosine is produced from phenylalanine and is found in cheeses, chicken, turkey, and fish. Tyrosine is important for the synthesis of dopamine, adrenaline, norepinephrine, thyroid hormones, and melanin. As a dietary supplement, it is purported to increase dopamine, adrenaline, and norepinephrine levels, thus improving memory and performance in stressful situations. In a very small study, 22 participants were given tyrosine or a placebo prior to a test to measure cognitive flexibility. Those getting the tyrosine supplement had improved performance on the test. Tyrosine may also be used in individuals with phenylketonuria (PKU), which is a rare genetic condition that results in the body's inability to create a specific enzyme, phenylalanine hydroxylase. The body uses this enzyme to convert phenylalanine into tyrosine, used in creating neurotransmitters. The treatment for PKU is to limit foods high in phenylalanine, resulting in a deficiency in tyrosine. Supplementation of tyrosine supplies the needed amino acid to avoid the behavioral problems that are associated with PKU. There are several medications that tyrosine interacts with, including monoamine oxidase inhibitors (MAOIs), thyroid hormones, and levodopa (Sinemet). A common dose is 500-2,000 mg (Van de Walle, 2018b). 

Taurine

Taurine may be taken for congestive heart failure (CHF), inflammation of the liver (hepatitis), athletic performance, boosting energy, chemotherapy-related nausea and vomiting, memory and cognitive function, cystic fibrosis, and diabetes. While there is insufficient evidence regarding taurine’s effectiveness for all of these uses, those with CHF report an increased ability to exercise with taurine use, and those with hepatitis show improved liver function with use. Taurine interacts with lithium (Lithobid) by decreasing how the body eliminates it, increasing lithium (Lithobid) levels and potentially resulting in toxicity and serious adverse effects. The suggested dose of taurine for CHF patients is 1.5 to 6 g/d in two to three divided doses. For hepatitis patients, the suggested dose is 1.5 to 4 g/d in two to three divided doses for up to three months (WebMD, n.d.f).

Probiotics

Probiotics are living microorganisms that have health benefits when consumed or applied to the human body. Sources include yogurt, dietary supplements, or beauty products. Most people consider bacteria or microorganisms as potentially harmful, yet many bacteria are beneficial in food digestion, produce vitamins, or help destroy disease-causing cells. The microorganisms in probiotic dietary supplements are similar to the microorganisms found on humans naturally. Probiotics contain several different microorganisms, but the most commonly used supplements belong to the groups Lactobacillus or Bifidobacterium. The yeast used as a probiotic is Saccharomyces boulardi. Approximately four million adults in the US used probiotics within a 30-day period in a 2012 survey according to the NCCIH (2019). They are the third most common dietary supplement behind vitamins and minerals. Probiotics work by helping the body maintain a healthy community of cooperative microorganisms or return to a healthy condition after an illness or the use of certain medications such as antibiotics. They influence the body's immune response and produce substances that support optimal GI health. While many studies related to probiotics are inconclusive, some areas of study have shown promise. Research has been favorable regarding the use of probiotics in the prevention of antibiotic-associated diarrhea, the prevention of necrotizing enterocolitis and sepsis in infants, the treatment of infant colic, or the treatment of periodontal disease. Other claims by manufacturers of probiotics are related to a decrease or prevention of allergies, skin conditions such as acne, dental caries, UTIs, and upper respiratory infections. Probiotics appear to be safe, with few, if any, adverse effects in healthy individuals. The risk of side effects goes up with immunocompromised patients or those with severe illnesses. Some probiotic supplements have been reported to contain microorganisms other than the ones listed on the label, and those contaminants could pose health risks (NCCIH, 2019).

Acidophilus

Lactobacillus acidophilus is a bacterium found in the human intestines and an ingredient found in fermented foods such as yogurt, sauerkraut, miso, tempeh, or dietary supplements. This organism aids in digestion and produces lactic acid by breaking down lactose. Other health benefits that have been substantiated through extensive studies include a reduction in cholesterol, reduction in diarrhea among hospitalized children, improved symptoms related to IBS, the treatment or prevention of vaginal infections, the promotion of weight loss when administered with other probiotics, reduction in cold and flu symptoms in children, reduction or prevention of allergy symptoms, prevention or reduction of eczema symptoms, and improved gut health.  While acidophilus is readily available in the aforementioned foods, it is also available in dietary supplements and should be taken with a meal, preferably breakfast (Robertson, 2017). 

Fish Oil

Fish oil is a dietary source of omega-3 fatty acids, which are polyunsaturated fatty acids needed for numerous body functions ranging from muscle activity to cellular growth. Specific functions include blood clotting, cell division and growth, and fertility. They are components of the phospholipid found in the cell membrane. Most fish oil supplements contain two omega-3 fatty acids: docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). DHA is found in higher concentrations in the brain, retina, and sperm and is needed for brain development and function. The primary dietary sources for DHA and EPA are cold-water fatty fish such as salmon, mackerel, trout, mussels, oysters, shellfish, and crabs.  Other foods such as eggs, yogurt, infant formula, and milk may be fortified with DHA and other omega-3s. Nuts, seeds, and vegetable oils (including flaxseed, soybean, and canola oils) also contain a third omega-3 fatty acid called alpha-linolenic acid (ALA). ALA is considered essential and must be obtained from food sources since the body cannot produce it. Similarly, EPA and DHA are mostly obtained from food sources as the body is only able to convert ALA into EPA and then DHA in very limited amounts (roughly 15%). In addition to dietary consumption, EPA and DHA can be supplemented via fish oil. Research supports the use of fish oil supplements to reduce the risk of cardiovascular disease (CVD), hypertension, elevated triglycerides or cholesterol, preterm delivery, and RA. Fish oil supplements are generally safe with minor side effects that include:

  • Bad breath,
  • Fishy aftertaste,
  • Nausea or indigestion,
  • Loose stools, 
  • Rash, or 
  • Increased risk of bleeding with high doses (Mayo Clinic, 2017; NIH, 2019). 

Omega-3 deficiency can lead to rough/scaly skin and dermatitis and is rare in the US. The Food and Nutrition Board, which establishes Dietary reference Intakes (DRIs) for vitamins and macronutrients, established the adequate intake (AI) for omega-3s to ensure nutritional adequacy, as the evidence was insufficient to establish a recommended daily allowance (RDA) or an estimated average requirement (EAR). In infants, the AI applies to total omega-3 intake; in individuals aged one year and above, the AI refers only to ALA as this is the only essential omega-3 (Table 1).

Three clinical trials were conducted on 898 pregnant women with high-risk pregnancies and a history of pre-term deliveries, intrauterine growth retardation (IGR), or pregnancy-induced hypertension. 579 women with high-risk twin pregnancies were included as part of the study. The women either received fish or olive oil, beginning between 20- and 33-weeks’ gestation through delivery. The women receiving the fish oil supplement had a 33% reduction in preterm delivery in comparison to a 21% reduction in those receiving the olive oil supplement. There was no impact on IGR or hypertension, however. The study concluded that fish oil supplementation reduced the risk of preterm delivery in high-risk pregnancies of single births, but found no significant difference in the twin pregnancy outcomes (Olsen et al., 2005).

Multiple studies have been done on the use of omega-3 fatty acids in the prevention of CVD, which stem from epidemiological studies that note a low rate of cardiovascular deaths among Arctic people. After studies found this could be associated with a diet high in seafood, additional research ensued. Supplemental EPA and DHA have been shown to reduce the risk of CVD, but the studies do not show that omega-3 fatty acid supplementation provides protection from CVD (NCCIH, 2017). A 2016 report from the Agency for Healthcare Research and Quality (AHRQ) found lower triglyceride and higher high-density lipoprotein (HDL) and low-density lipoprotein (LDL) levels related to increased omega-3 intake; they found no correlating effect on major adverse cardiovascular events. A meta-analysis done in 2018 found that daily supplementation (376-2,550 mg of EPA and DHA daily) found no reduction in risk of fatal CVD, acute myocardial infarction, stroke, or other major vascular event. Researchers cite a general increase in omega-3 consumption as a possible explanation for a lack of significant reduction in risk in these more recent studies, indicating a possible threshold or plateau effect from omega-3s. Another explanation is the confounding concurrent use of statins and other cardioprotective therapies (NIH, 2019).

Studies on the use of omega-3 fatty acids in both seafood and fish oil supplements show some improvement in RA symptoms such as morning stiffness, joint pain, and swelling. There was a decreased requirement for the use of anti-inflammatory drugs for RA based on a 2012 systematic review (NCCIH, 2017). 

DHA is vital to brain and ophthalmic functioning. While there is no current evidence regarding its effectiveness, it is suggested that omega-3 fatty acids may impact conditions involving the brain or eyes. Areas of future or pending research in regard to fish oil supplementation include ADHD, depression, bipolar disorder, autism, schizophrenia, asthma, cancer-related cachexia, cystic fibrosis, lupus, osteoporosis, and Crohn's disease (NCCIH, 2017).

Possible drug interactions for fish oil include anticoagulants such as warfarin (Coumadin), antihypertensives (resulting in severe hypotension), contraceptive drugs (making the fish oil less effective on triglycerides), orlistat (Alli), (which might cause a decreased absorption of the fatty acids and should be taken two hours apart), and vitamin E (fish oil may reduce vitamin E levels). Vegetarians may choose to take vegetable-based supplements such as flaxseed or algae oils for EPA and DHA (Mayo Clinic, 2017). Overall, fish oils are considered safe, yet there are potential concerns. Some fish oils contain vitamins A and D, and at high levels, these can be toxic and should be considered when taking other supplements, particularly fat-soluble vitamins. Some evidence suggests that fish oil supplementation could increase the risk of prostate cancer. Finally, it is not established whether fish oil supplements are safe for those with seafood or shellfish allergies and should be used with caution (NCCIH, 2017).  


Botanicals/Herbs

Dietary Supplement and Dosing Information

Potential Benefits

Implications/Alerts

Black cohosh should be Dosed from 6.5 to 160 mg/d, with a median dose of 40 mg/d.

Promoted for menopausal symptoms, sleep disturbances, irritability, or heart palpitations.

  • Limit use to six months or less due to risk of liver damage with long term use or high doses
  • Instruct patients to report abdominal pain, dark urine, or jaundice
  • Not advices for patients with estrogen-receptive positive cancers (i.e. breast cancer)

Echinacea should be dosed from 2400-4000 mg/d.

Prevention or treatment of infections such as the common cold. Topical use for skin wounds or conditions. May boost the human immune system.

  • Short term use is considered safe, but long-term safety is not proven
  • Common adverse effects include nausea, stomach pain, or allergic reaction 
  • No significant drug interactions

Garlic dosing is based on indication:

  • 1000-7200 mg/d for hyperlipidemia
  • 300-1500 mg/d for hypertension (HTN)
  • 1 mg/kg/d for cancer prevention


Prevention of common cold, colon, and stomach cancers. 

Treatment for HTN and hyperlipidemia.

  • May interact with blood thinners such as warfarin (Coumadin), antiviral drugs such as saquinavir (Invirase) and ritonavir (Norvir)

Ginkgo biloba should be dosed from 120-240 mg/d.

Promoted for dementia, intermittent claudication, eye problems, or tinnitus.

  • Increased risk of bleeding with concurrent use of warfarin (Coumadin)
  • Use with caution in pregnancy due to increased risk of bleeding
  • Increased risk of liver and thyroid cancers
  • Avoid consumption of seeds of the plant due to toxicity

Saw palmetto should be dosed from 160-230 mg/d.

Promoted for treatment of enlarged prostate, chronic pelvic pain, migraines, hair loss, or decreased sex drive.

  • Use with caution in pregnancy and breastfeeding
  • No significant drug interactions

St. John's wort should be dosed from 750-900 mg/d.

Promoted for depression, menopausal symptoms, ADHD, IBS, OCD, and topically for wound healing.

  • Can decrease the effectiveness of HIV drugs, cancer drugs such as irinotecan HCL (Camptosar), SSRIs, cyclosporine (Neoral), digoxin (Lanoxin), birth control pills, warfarin (Coumadin) 
  • Monitor for suicidal ideations in patients taking St. John's wort for depression

(Kubala, 2018; NCCIH, 2016a, 2016b, 2016c, 2016d, 2016e; NIH, 2011, 2018)

Amino Acids

Dietary Supplement and Metabolic Role

Typical Dosing

Implications/Alerts

Phenylalanine plays a vital role in the structure and function of proteins and enzymes; it is also a precursor for neurotransmitters.

33 mg/kg/d

  • Phenylalanine can act as a neurotoxin at high levels

Valine stimulates muscle growth and regeneration; it is also involved in energy production.

24 mg/kg/d

  • Avoid use with levodopa (Sinemet, Inbrija) as it may decrease absorption.
  • May decrease blood glucose, avoid use with antidiabetic medications, could produce hypoglycemia

Threonine decreases constant or unwanted muscle contractions.

20 mg/kg/d

  • Used in disorders marked by muscle tightness and involuntary movements such as MS or Lou Gehrig's disease

L-tryptophan is required for serotonin production, which regulates mood, behavior, and sleep.

5 mg/kg/d

  • May be effective with smoking cessation, teeth grinding and myofascial pain syndrome


Methionine is involved in the production of cysteine, which builds proteins.

19 mg/kg/d

  • Taken for liver disorders or viral infections
  • Taken after acetaminophen (Tylenol) overdose to prevent liver damage
  • Taken to reduce risk of breast and colon cancer, neural tube defects, and hot flashes
  • Suggested treatment for HPV, HSV, pancreatitis, depression, alcohol use disorder, allergies, asthma, radiation side effects, schizophrenia, drug withdrawal, or UTIs

Leucine is crucial for muscle repair and protein synthesis.

42 mg/kg/d

  • Helps regulate blood glucose levels
  • Produces growth hormones
  • Stimulates wound healing

Isoleucine induces muscle protein synthesis.

19 mg/kg/d

  • Increases glucose uptake during exercise
  • Used as a performance enhancer by athletes
  • Important for immune function, energy regulation, and hemoglobin production

Lysine is involved in protein synthesis, hormone production, enzyme production, and absorption of calcium.

38 mg/kg/d

  • Involved in collagen and elastin production
  • Increased energy production
  • Improved immune function

Histidine is a precursor for several hormones and critical metabolites affecting renal function, neurotransmission, gastric secretion, and immune function

14 mg/kg/d

  • Used for metabolic syndrome, diarrhea related to cholera infection, RA, gastric ulcers, anemia associated with renal failure, and allergic conditions

Branched-chain amino acids (BCAAs) have five benefits: increased muscle growth, decreased muscle soreness, reduction in exercise fatigue, prevention of muscle wasting, and improvement in liver disease such as cirrhosis.

200-240 mg/kg/day

  • Avoid during pregnancy and breastfeeding as there is insufficient information to support the use or implications
  • Patients with ALS should avoid use as there is an increased rate of respiratory failure with use
  • Avoid use with branched chain ketoaciduria as seizures can result
  • Can interfere with blood glucose levels, particularly in infants or during surgery

Glutamine plays a critical role in the immune system and GI health.

35-50 mg/kg/d

  • Can decrease risk for infection, improve overall health, and shorten hospital stays in comparison to placebos
  • Used with burn patients and serious infections with improved outcomes
  • Body builders use to decrease fatigue and muscle soreness after exercise

Aspartate increases the absorption of minerals and may improve athletic performance.

No recommended dietary intakes listed

  • May be used with liver failure to slow brain damage
  • Often combined with minerals to improve absorption, such as copper aspartate

L-arginine is involved in wound healing, maintaining immune and hormone function, and helps blood vessels relax and improves circulation.

2000-3000 mg/d

  • Used in the treatment of HTN (including during pregnancy), angina, peripheral artery disease, and erectile dysfunction
  • May interact with captopril (Capoten), enalapril (Vasotec), diltiazem (Cardizem), nitroglycerin (Nitro-Bid, Nitro-Dur, (Nitrostat), isosorbide (Imdur, Isordil), or Sildenafil (Viagra), causing hypotension.


Ornithine is thought to increase the levels of arginine; it may also elevate hormone levels associated with increased muscle size.

2000 mg/d for 7 days, then 3000 mg prior to exercise; 1000 mg/d may be taken in combination with arginine routinely

  • Primarily used for performance enhancement in athletes
  • May be used for weight loss, improved sleep quality, or wound healing, but limited evidence to support

Tyrosine is made from phenylalanine within the body; it is involved in protein production.

500-2000 mg/d in most adults;

up to 7600 mg/d to treat PKU

  • Most commonly used to treat PKU since these individuals cannot consume foods high in phenylalanine, resulting in a tyrosine deficiency
  • May interact with MAOIs, thyroid hormones, and levodopa (Sinemet)

Taurine is involved in brain and nerve growth, and appears to calm the sympathetic nervous system

1500-6000 mg/d

  • May interact with lithium (Lithobid), causing toxic serum levels
  • Most commonly used for liver inflammation (hepatitis), cystic fibrosis, diabetes, athletic performance, boosting energy, chemotherapy-related nausea and vomiting, and memory or cognitive functioning

(Kubala, 2018; Menayang, 2018; NLM, n.d., 2020; Patel, 2019; RxList, n.d.; Tinsley, 2018; Van de Walle, 2018a; Van de Walle, 2018b; WebMD, n.d.a, n.d.b, n.d.c, n.d.d, n.d.e, n.d.f, n.d.g)

Probiotics

Dietary Supplement and Therapeutic Role

Typical Dosing

Implications/Alerts

Lactobacillus acidophilus is a bacterium found in the human intestines and an ingredient in fermented foods such as yogurt, sauerkraut, miso, tempeh, or dietary supplements;

 it aids in digestion and produces lactic acid by breaking down lactose

1-2 capsules per day; or 1-10 billion colony forming units (CFU) in three to four divided doses

  • Common side effects include bloating and flatulence (gas)
  • Associated with a reduction in cholesterol and weight loss; decreased diarrhea among hospitalized children; improved IBS symptoms; and treatment or prevention of vaginal infections, particularly after antibiotic use

(Robertson, 2017)

Fish Oil

Dietary Supplement and Therapeutic Role

Typical Dosing

Implications/Alerts

Omega-3 fatty acids are needed for numerous body functions ranging from muscle activity to cellular growth, such as clotting of blood, cell division and growth, and fertility. Uses include prevention of heart disease, improvement of RA symptoms, as well as improved brain and eye functioning


The adequate intake (AI) of ALA is 0.5-1.2 g in infants/children and 1.1-1.6 in adolescents/adults. 

Typically, a 1 g fish oil supplement provides approximately 300 mg of combined EPA and DHA.

  • DHA and EPA can be found in fish oil supplements, as well as salmon, mackerel, trout, and shellfish.
  • The only essential omega-3 fatty acid (ALA) is found in plant-based sources such as nuts, seeds, and vegetable oils.
  • Side effects include bad breath, fishy aftertaste, nausea, indigestion, loose stools, or rash; elevated risk of bleeding with increased doses
  • May interact with anticoagulants such as warfarin (Coumadin), antihypertensive medications (resulting in severe hypotension), contraceptive drugs (making the fish oil less effective on triglycerides), orlistat (Alli, which might decrease the absorption of the fatty acids and should be taken two hours apart), and vitamin E (fish oil may reduce vitamin E levels)
  • Use with caution in those with an allergy to shellfish

(NCCIH, 2017; NIH, 2019)

References

Kubala, J. (2018). Essential amino acids: Definition, benefits, and food sources. Healthline. https://www.healthline.com/nutrition/essential-amino-acids

Mayo Clinic. (2017). Fish oil. https://www.mayoclinic.org/drugs-supplements-fish-oil/art-20364810

Memorial Sloan Kettering Cancer Center. (2020). Black cohosh. https://www.mskcc.org/cancer-care/integrative-medicine/herbs/black-cohosh

Menayang, A. (2018). Leucine intake from a supplement may be better for muscle protein synthesis than leucine from a meal. https://www.nutraingredients-usa.com/Article/2018/10/19/Leucine-supplement-fared-better-than-leucine-from-meal-for-muscle-building

The National Center for Complimentary and Integrative Health. (2016a). Echinacea. https://www.nccih.nih.gov/health/echinacea

The National Center for Complimentary and Integrative Health. (2016b). Garlic. https://www.nccih.nih.gov/health/garlic

The National Center for Complimentary and Integrative Health. (2016c). Ginkgo. https://www.nccih.nih.gov/health/ginkgo

The National Center for Complimentary and Integrative Health. (2016d). Saw palmetto. https://www.nccih.nih.gov/health/saw-palmetto

The National Center for Complimentary and Integrative Health. (2016e). St. john’s wort. https://www.nccih.nih.gov/health/st-johns-wort

The National Center for Complementary and Integrative Health. (2017). Omega-3 supplements: In depth. https://nccih.nih.gov/health/omega3/introduction.htm

The National Center for Complimentary and Integrative Health. (2019). Probiotics: What you need to know. https://www.nccih.nih.gov/health/probiotics-what-you-need-to-know

The National Institutes of Health. (2011). Botanical dietary supplements. https://ods.od.nih.gov/factsheets/BotanicalBackground-HealthProfessional/

The National Institutes of Health. (2018). Black cohosh. https://ods.od.nih.gov/factsheets/BlackCohosh-HealthProfessional/

The National Institutes of Health. (2019). Omega-3 fatty acids. https://ods.od.nih.gov/factsheets/Omega3FattyAcids-HealthProfessional/

Olsen, S.F., Seecher, N.J., Tabor, A., Weber, T., Walker, J., & Gluud, C. (2005). Randomized clinical trials of fish oil supplementation in high risk pregnancies. BJOG, 107(3), 382-395. https://doi.org/10.1111/j.1471-0528.2000.tb13235.x

Patel, K. (2019). Valine. https://examine.com/supplements/valine/

Robertson, R. (2017). 9 ways lactobacillus acidophilus can benefit your health. https://www.healthline.com/nutrition/lactobacillus-acidophilus

RxList. (n.d.). Aspartates. Retrieved on April 25, 2020, from https://www.rxlist.com/aspartates/supplements.htm

Tinsley, G. (2018). Glutamine: Benefits, uses, and side-effects. Healthline. https://www.healthline.com/nutrition/glutamine

US National Library of Medicine. (n.d.). Phenylalanine. Retrieved April 26, 2020, from https://pubchem.ncbi.nlm.nih.gov/compound/L-phenylalanine

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

US National Library of Medicine. (2020a). Amino acids. https://medlineplus.gov/ency/article/002222.htm

US National Library of Medicine. (2020b). Herbs and supplements. https://medlineplus.gov/druginfo/herb_All.html

Van de Walle, G. (2018a). 5 proven benefits of BCAAs (branch-chain amino acids). Healthline. https://www.healthline.com/nutrition/benefits-of-bcaa

Van de Walle, G. (2018b). Tyrosine: Benefits, side effects and dosage. Healthline. https://www.healthline.com/nutrition/tyrosine

WebMD. (n.d.a). Arginine. Retrieved April 25, 2020, from https://www.webmd.com/vitamins/ai/ingredientmono-875/l-arginine

WebMD. (n.d.b). Histidine. Retrieved April 24, 2020, from https://www.webmd.com/vitamins/ai/ingredientmono-467/histidine

WebMD. (n.d.c). L-tryptophan. Retrieved April 24, 2020, from https://www.webmd.com/vitamins/ai/ingredientmono-326/l-tryptophan

WebMD. (n.d.d). Methionine. Retrieved April 24, 2020, from https://www.webmd.com/vitamins/ai/ingredientmono-42/methionine

WebMD. (n.d.e). Ornithine. Retrieved April 25, 2020, from https://www.webmd.com/vitamins/ai/ingredientmono-200/ornithine

WebMD. (n.d.f). Taurine. Retrieved April 24, 2020, from https://www.webmd.com/vitamins/ai/ingredientmono-1024/taurine

WebMD. (n.d.g). Threonine. Retrieved April 24, 2020, from https://www.webmd.com/vitamins/ai/ingredientmono-1083/threonine