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Safe Supplements—Plant Derived and Non

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Plant extracts have been used for centuries for their restorative, psychoactive, or healing properties. Nearly half of all pharmaceuticals are derived from plants. It is estimated that 80% of the plant-derived pharmaceuticals target ailments that the plant itself was historically used to treat.[1] It is common for patients to take a combination of conventional pharmaceuticals and plant-derived supplements in treatment or preventative protocols. The efficacy of many pharmaceuticals is due to their chemical component originally derived from plants. Plants evolved for thousands of years to make complex secondary metabolites to protect themselves from herbivory. Supplements are not always safe just because they are plant-derived. Below is an overview of some common supplements (some, but not all of which are plant-derived) and their hypothesized efficacy and potential interactions.

Note: The following information is not a comprehensive analysis of every possible supplement, herb, and medication interaction. Always use caution and consult your health care provider before combining medications and supplements.

St. John’s Wort

Hypericum perforatum

St. John’s Wort is an herbal supplement most commonly used to treat depression. Studies have been conducted on St. John’s Wort and found it to be more effective than placebos at alleviating depression. Some researchers have even claimed that the herb is comparable to conventional antidepressants. The plant has been used for centuries for various uses such as wound healing and treatment of anxiety and depression. In fact, there is evidence that Hippocrates recommended St. John’s Wort to treat snake bites. Hypericin (a component of St. John’s Wort extract) binds to adenosine receptors, GABA receptors, and receptors that regulate dopamine levels. Hyperforin (another component of St. John’s Wort extract) is a reuptake inhibitor of dopamine, serotonin, norepinephrine, GABA, and glutamate. Hypericin and hyperforin are likely accountable for the effectiveness of St. John’s Wort in alleviating depression. While this supplement may have some antidepressant and healing effects, it is important to take it with caution. St. John’s Wort has been shown to affect the metabolism of half of all pharmaceuticals. Moreover, it affects more drugs than any other known botanical supplement.

How? St. John’s Wort has several biologically active components, such as hypericin and hyperforin. Once ingested and digested, the hyperforin in St. John’s Wort will bind to steroid xenobiotic receptors (SXR) on cells. The resulting compound (hyperforin + SXR) then travels to the nucleus of cells where it promotes transcription of enzymes responsible for metabolizing drugs, such as cytochrome p450 enzymes CYP3A4 and CYP1A2. Thus, many drugs taken with St. John’s Wort get metabolized more readily and rapidly. [2],[3]

St. John’s Wort is known to interact with certain pharmaceuticals and supplements, which include, but are not limited to:

o   Immunosuppressants

o   Chemotherapy

o   Oral/steroidal contraceptives

o   Antihistamines

o   Antidepressants

o   Benzodiazepines

o   Antihypertensives

o   Anticoagulants

o   HIV medications

o   Antifungals

o   Dozens of herbs, including: Ashwagandha, Siberian ginseng, lemon balm, chamomile, cranberry extract

Ginkgo

Ginkgo biloba

Ginkgo is a type of tree, often known for its interesting fan-shaped leaves and unfortunate scent. It is considered a “living fossil”, as it is one of the oldest living trees (150 million years old!). The leaf extract from ginkgo has been used for centuries to improve cognitive ailments. Ginkgo leaf extract contains varying amounts of ginkolinic acid depending on the age, time of year, and health of the tree at the time of collection. The extract must be standardized to ensure a low enough concentration of ginkolinic acid, as this chemical is toxic and will cause allergic reaction or gastrointestinal upset. The pharmacologically active components of ginkgo leaf extract are types of flavonoids and terpenoids. These have been shown to have powerful antioxidant effects. Ginkgo extract may also decrease the expression of benzodiazepine receptors and decrease the level of circulating glucocorticoids. Ginkgo selectively inhibits cytochrome p450 enzymes and has several drug interactions. [4]

Ginkgo is known to interact with certain pharmaceuticals and supplements, which include, but are not limited to:

o   Anticoagulants

o   Antiepileptics

o   Antidiabetics

o   Diuretics

o   NSAIDs

Curcumin

Curcuma longa

Curcumin is a component of the spice turmeric from the Asian plant Curcuma longa. Turmeric has been used in traditional Asian cooking and medicine for centuries, and is now often an additive in foods for its brilliant yellow pigmentation. Nearly every population in the world consumes some form of curcumin daily, with Asian countries consuming the most. Curcumin, or diferuloyl methane, comes from the dried rhizome (underground stem) of the turmeric plant. Curcumin has gained popularity as a supplement for its many health benefits. It is a potent antioxidant, anti-inflammatory, and has even been shown to have antidepressant effects. Zingiberen and tumerone, two volatile oils from turmeric, have antispasmodic and antibiotic effects. Curcumin, like many other herbal supplements, also inhibits cytochrome p450 and may slow drug metabolism. Studies have shown that salivary cortisol levels are lower in patients supplementing with curcumin. Overall, curcumin is very safe and beneficial to take as a supplement or as part of the diet. It may, however, inhibit the tumor-killing properties of some chemotherapy drugs and cause excess bleeding if taken with NSAIDs. [5],[6],[7]

Curcumin is known to interact with certain pharmaceuticals and supplements, which include, but are not limited to:

o   NSAIDs

o   Acetaminophen

o   Chemotherapy (specifically breast cancer chemotherapy)

o   Antacids

Eleuthero | Siberian Ginseng

Eleutherococcus senticosus

Siberian ginseng is a plant in the same family as other ginsengs, but is not technically a ginseng itself. It is called Siberian ginseng because of its similar adaptogenic qualities to Panax ginseng. Siberian ginseng (Eleutherococcus senticosus, sometimes just called Eleuthero) contains triterpene saponins called eleutherosides responsible for its medicinal effects. Eleuthero has adaptogenic, antiviral, and antioxidant effects. It has been shown to increase T-cell number and activity, which boosts immunity. It also has been shown to reduce LDL cholesterol (“bad” cholesterol) and lower blood sugar. Long-term use of Eleuthero is the most effective, as in small doses over just a few days it may not have any health benefit. There are very few known interactions with Siberian ginseng. [8],[9],[10]

Eleuthero is speculated to interact with certain pharmaceuticals and supplements, which include, but are not limited to:

o   Low blood pressure medications

o   Digoxin

o   Sleep aids

o   Antidiabetics

Panax | Ginseng

Panax ginseng & Panax quinquefolius

When people refer to a supplement as simply “ginseng”, they are likely talking about Panax ginseng. Panax ginseng and P. quinquefolius are two species of ginseng in the Panax genus commonly used as herbal remedies. In fact, ginseng is one of the most broad-reaching, powerful, and variable supplements. It has been used for thousands of years and the first known mention of its use medicinally dates back to 3000 B.C.E. The root of the plant, which is the part used medicinally, is known for its appearance- it looks like a little person. The word ginseng comes from the Chinese phrase “jen shen”, meaning man root. Ginseng is an adaptogen, capable of increasing cellular energy and helping cells utilize energy without over or under stimulation. The term “adaptogen” was actually invented when no other adjective accurately encompassed the power of ginseng. The medicinally active components of ginseng are compounds called ginsenosides. These have been shown to lower blood sugar and blood pressure, increase libido and stamina, and improve menopausal symptoms. Some studies even show a 60% reduction in cancer likelihood with long term ginseng supplementation. Ginseng is relatively safe but does have some potential side effects or interactions. [11],[12]

Ginseng is known to interact with certain pharmaceuticals, supplements, and substances which include, but are not limited to:

o   Blood thinning agents

o   Stimulants

o   Caffeine

o   Phenelzine (and likely all MAOIs)

o   Alcohol

5-HTP

Griffonia simplicifolia

5-HTP is a supplement commonly taken to improve mood, alleviate depression, assist in satiety, and aid in sleep. In the human body, 5-HTP is converted to serotonin via the enzyme dopa decarboxylase. Serotonin is responsible for excitatory regulation in the brain, pain perception, sleep, digestion, hormonal balance, cravings, and mood. Supplemental 5-HTP often comes from the African plant Griffonia simplicifolia. The seeds of G. simplicifolia contain high concentrations of 5-HTP, a naturally occurring amino acid. In the body, 5-HTP is produced from the essential amino acid tryptophan. Humans cannot synthesize their own tryptophan and must get it from the diet. Supplementing with 5-HTP is often a safe and natural way to boost serotonin levels and possibly improve related symptomology. Extreme excesses in serotonin, though, can be problematic and lead to a rare but dangerous condition called serotonin syndrome. It is important to supplement 5-HTP with caution when combined with other serotonergic medications to prevent the risk of developing serotonin syndrome. [13],[14]

5-HTP is known to interact with certain pharmaceuticals and supplements, which include, but are not limited to:

o   Migraine medications

o   Antidepressants

o   Tramadol

o   Cough syrups

o   Anti-anxiety medications

SAMe

S-Adenosylmethionine

S-adenosylmethionine, or SAMe (pronounced sam-ee), is a compound found in all living organisms. SAMe is the primary methyl donor for many metabolic pathways and a structural component of cell membranes. SAMe in humans comes from dietary methionine, which is activated by ATP. SAMe is taken as a supplement to help with depression, joint pain, and fatigue. The body has to eliminate methylation end products efficiently and quickly for healthy methylation to take place. Betaine, folate, and vitamin B12 are necessary for this elimination process and to regenerate methionine from SAMe, so SAMe is best utilized in the body when combined with these necessary cofactors. SAMe also degrades very quickly, and many methylation support products containing SAMe contain degraded and inactive forms of SAMe. Methylation support formulas should be chosen carefully to ensure that the SAMe is bioavailable and that necessary cofactors are included. SAMe can interfere with some medications, rendering them more or less effective. [15],[16]

SAMe is known to interact with certain pharmaceuticals and supplements which include, but are not limited to:

o   Antidepressants

o   Tramadol

o   Cough syrups

o   Levodopa

Passion Flower

Passiflora incarnata

The passion flower, or Passiflora spp. is known for its magnificent flowers and healing properties. It is found mostly in tropical regions, and there are hundreds of species of passion flowers. P. incarnata is the species widely used medicinally. The plant was popularized in Europe in the 19th century as a Christian symbol, and named passion flower in reference to the crucifixion of Christ. The flowers became popular in tinctures and teas for alleviation of anxiety, depression, and digestive upset. The sedative and tranquilizing properties of passion flower have been recognized for decades, but it was only recently that the mechanism of action of passion flower was uncovered. The flavonoids in P. incarnata work on the gabaminergic system. GABA agonists such as benzodiazepines or alcohol are widely known and consumed for their sedative effects. Evidence suggests that passion flower flavonoids bind to both GABAA and GABAB receptors, unlike alcohol and benzodiazepines which only affect GABAA receptors. GABAB receptor antagonism can alleviate concerns with addictive substance withdrawal, insomnia, and anxiety. The exact mechanism with which passion flower modulates the gabaminergic system is still being studied. Passion flower has also been shown to be effective in improving concerns with ADHD, cancer, diarrhea, and stomach pain. There are very few contraindications with passion flower supplementation. [17],[18],[19]

o   Passion flower may increase the tranquilizing effects of other sedatives such as alcohol, antidepressants, and anti-anxiety medications

Resources

[1] Veeresham, C. (2012). Natural products derived from plants as a source of drugs. Journal of Advanced Pharmaceutical Technology & Research, 3(4), 200. doi:10.4103/2231-4040.104709
[2] St. John’s Wort and Depression: In Depth. (2016, May 05). Retrieved May 19, 2017, from https://nccih.nih.gov/health/stjohnswort/sjw-and-depression.htm
[3] Klemow KM, Bartlow A, Crawford J, et al. Medical Attributes of St. John’s Wort (Hypericum perforatum) In: Benzie IFF, Wachtel-Galor S, editors. Herbal Medicine: Biomolecular and Clinical Aspects. 2nd edition. Boca Raton (FL): CRC Press/Taylor & Francis; 2011. Chapter 11. Available from: https://www.ncbi.nlm.nih.gov/books/NBK92750/
[4] Mahadevan, S. and Park, Y. (2008), Multifaceted Therapeutic Benefits of Ginkgo biloba L.: Chemistry, Efficacy, Safety, and Uses. Journal of Food Science, 73: R14–R19. doi:10.1111/j.1750-3841.2007.00597.x
[5] Yu, J., Pei, L., Zhang, Y., Wen, Z., & Yang, J. (2015). Chronic Supplementation of Curcumin Enhances the Efficacy of Antidepressants in Major Depressive Disorder. Journal of Clinical Psychopharmacology, 1. doi:10.1097/jcp.0000000000000352
[6] Somasundaram, S., Edmund, N.A., Moore, D.T., Small, G.W., Shi, Y.Y. and Orlowski. R.Z. (2002). Dietary curcumin inhibits  chemotherapy-induced apoptosis in models of human breast cancer. Cancer Research, 62(13), 3868-3875.
[7] Abebe, W. (2002). Herbal medication: potential for adverse interactions with analgesic drugs. Journal of Clinical Pharmacy and Therapeutics, 27(6), 391-401. doi:10.1046/j.1365-2710.2002.00444.x
[8] Edwards, S. E., Costa Rocha, I. D., Williamson, E. M., & Heinrich, M. (2015). Phytopharmacy: an evidence-based guide to herbal medicinal products (pp. 177-179) (S. E. Edwards, I. Rocha, E. M. Williamson, & M. Heinrich, Authors). Chichester, West Sussex, UK: Wiley Blackwell.
[9] McRae, S. (1996). Elevated serum digoxin levels in a patient taking digoxin and Siberian ginseng. CMAJ: Canadian Medical Association Journal, 155(3), 293–295.
[10] Castleman, M. (2009). 130 Healing Herbs. In The New Healing Herbs (pp. 201-204).
[11] Coon, J.T. & Ernst, E. Drug-Safety (2002) 25: 323. doi:10.2165/00002018-200225050-00003
[12] Castleman, M. (2009). 130 Healing Herbs. In The New Healing Herbs (pp. 250-259).
[13] Subbaraju, G. V., Kannababu, S., Vijayakumar, K., Murthy, P. B., Vanisree, M., & Tsay, H. (2005). Spectrophotometric Estimation of L- 5-Hydroxytryptophan in Griffonia simplicifolia Extracts and Dosage Forms. International Journal of Applied Science and Engineering, 3(2), 111-116.
[14] 5-Hydroxytryptophan (5-HTP). (n.d.). Retrieved May 23, 2017, from http://www.umm.edu/health/medical/altmed/supplement/5hydroxytryptophan-5htp
[15] And, C. S. (2002, November 01). S-Adenosylmethionine: molecular, biological, and clinical aspects—an introduction. Retrieved May 23, 2017, from http://ajcn.nutrition.org/content/76/5/1148S.full?related-urls=yesl76%2F5%2F1148S
[16] Possible Interactions with: S-Adenosylmethionine (SAMe). (n.d.). Retrieved May 23, 2017, from http://www.umm.edu/health/medical/altmed/supplement-interaction/possible-interactions-with-sadenosylmethionine-same
[17] Appel, K., Rose, T., Fiebich, B., Kammler, T., Hoffmann, C., & Weiss, G. (2010). Modulation of the γ-aminobutyric acid (GABA) system by Passiflora incarnata L. Phytotherapy Research, 25(6), 838-843. doi:10.1002/ptr.3352
[18] Grundmann, O., Wang, J., Mcgregor, G., & Butterweck, V. (2008). Anxiolytic Activity of a Phytochemically CharacterizedPassiflora incarnataExtract is Mediated via the GABAergic System. Planta Medica, 74(15), 1769-1773. doi:10.1055/s-0028-1088322
[19] Castleman, M. (2009). 130 Healing Herbs. In The New Healing Herbs (pp. 358-360).

Clinical Contributor

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Disclaimer: The information provided is only intended to be general educational information to the public. It does not constitute medical advice. If you have specific questions about any medical matter or if you are suffering from any medical condition, you should consult your doctor or other professional healthcare provider.

Ramona Richard, MS, NC

Ramona Richard, MS, NC

Ramona Richard graduated with honors from the University of California with a Bachelor’s Degree in psychology and graduated summa cum laude with a Master’s Degree in Health and Nutrition Education. She also holds a Standard Designated Teaching Credential from the State of California, is a California state-certified Nutrition Consultant and a member of the National Association of Nutrition Professionals.

Ramona has participated in nutrition education in both public and private venues, including high school and college presentations, radio and public speaking for the past 20 years. She is the owner of Radiance, a nutrition consulting company, the Director of Education for Sanesco International, and a medical technical writer.

Disclaimer: The information provided is only intended to be general educational information to the public. It does not constitute medical advice. If you have specific questions about any medical matter or if you are suffering from any medical condition, you should consult your doctor or other professional healthcare provider.

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