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Herbs & Lab Tests

Recent surveys indicate that more than 50% of the population use some form of complementary and alternative medicine. In the United States, the sale of herbal medicines now exceeds $4 billion per year. Marketing campaigns often imply that any natural product is safe. However, herbal medicines are classified as dietary supplements and do not have to be proven safe before being released into the marketplace. Many herbs have been associated with adverse effects due to: Abnormal results may occur by any of the following mechanisms:

  • Assay interference
  • Herb-therapeutic drug interaction
  • Organ toxicity
  • The most common abnormalities are summarized below.

 

Common Name

Other Names

 

Intended Use

 

Adverse Effects

 

Aristolochic Acid

Snakeroot, birthroot, snakeweed, sangree root, serpentary, wild ginger

traditional Chinese herbs

nephrotoxicity, carcinogenic

Bitter Orange

Citrus aurantium, zhi xhi, zhi oiao, zhiqiao, kijitsu, neroli oil, Shangzhou,

weight loss, stimulant, athletic performance

tachycardia, vasoconstriction, hypertension, stroke

Borage oil

Borago officinalis, bee plant, bee bread, ox’s tongue, starflower oil

rheumatoid arthritis, hypertension

hepatotoxicity, lower seizure threshold, increase warfarin effect

Cat's Claw

Uncaria tomentosus, Una de gato, hawks claw

anti-viral, prevent colds & flu, chronic fatigue syndrome

hypotension, diarrhea, increase warfarin effect, inhibit CYP3A4

Chan Su

Chinese toad auricular glands

tonsillitis, sore throat, palpitations, heart tonic

vasoconstriction, hypertension, arrhythmia, digoxin immunoreactivity

Chaparral

Larrea tridentata, creosote bush, jarilla, greasewood, hediondilla

anti-neoplastic, anti-oxidant, arthritis remedy, cleansing tonic

cholestatic hepatotoxicity, nephrotoxicity, carcinogenic

Comfrey

Symphytum officinale, knitbone, nipbone, black root, bruisewort, consolidae radix

inflamed joints, wounds, gout, fractures, thrombophlebitis

hepatic veno-occlusive disease

Dan Shen

Salvia miltiorrhiza

angina pectoris, cardiovascular diseases

digoxin immunoreactivity, increase warfarin effect, platelet inhibition, fibrinolysis

Dong quai

Angelica senensis

menopause & menstruation

increase warfarin effect

Echinacea

Purple cone flower

colds, flu, URI, UTI, immune stimulant

allergic reactions, nausea, myalgia, hepatitis

Ephedra

Ma huang

weight loss, stimulant, athletic performance

arrhythmia, hypertension, stroke

Evening Primrose

Oenothera biennis, primrose oil

breast tenderness, PMS

lower seizure threshold

Feverfew

Tanacetum parthenium, Chrysanthemum

headaches, migraines, menstrual cramps, arthritis

increase warfarin effect

Garlic

Allium sativum

lower blood pressure & cholesterol

increase warfarin effect, platelet inhibition

Germander

Teucrium chamaedrys

weight loss, general tonic

cholestatic hepatotoxicity

Ginger

motion & morning sickness

increase warfarin effect

Ginkgo biloba

Maiden hair tree

forgetfulness, mental focus, tinnitus, claudication

increase warfarin effect, platelet inhibition, hypertension, seizures

Ginseng

Eleutherococcus senticosus (Siberian), Panax ginseng (Asian)

stress, endurance

decrease warfarin effect, digoxin immunoreactivity, hypoglycemia, Stevens Johnson, schizophrenia

Green tea

Camellia sinensis

cancer prevention, heart tonic, nausea & vomiting

decrease warfarin effect

Kava kava

Piper methysticum, kawa, ava, awa, gea ,gi, kao, kew, malohu, yagona, sakau

anxiety, insomnia

hepatoxicity, parkonsonism, GABA receptor blockade, calcium & sodium channel blockade

Kelp

anti-inflammatory, thyroid tonic, metabolic tonic

hyperthyroidism

Licorice root

anti-inflammatory, peptic ulcers

aldosteronism, hypokalemic myopathy, hypertension, increase warfarin effect

 

Lobelia

Lobelia inflata, Pokeweed, Indian tobacco, cardinal flower, asthma weed

 

anti-viral, anti-neoplastic

 

arrhythmia, respiratory failure

Lu Shen Wan

heart tonic

falsely elevated digoxin levels

Mistletoe

digestive aid, sedative, heart tonic

hepatotoxicity

Moonflower

Daturia inoxia

hallucinogen

seizures, hallucinations, coma

Oleandrin

Nerium oleander, dogbane, Thevetia peruviana, rose laurel

cancer, HIV, hepatitis, psoriasis, rheumatoid arthritis

arrhythmia, contact dermatitis, digoxin immunoreactivity, N&V, diarrhea, salivation, altered mentation

Passion flower

Passiflora incarnata

insomnia, anxiety

arrhythmia, drowsiness

Pennyroyal

Mentha puleguim, Hedeoma pulegoides, squawmint, mosquito plant, tickweed

induce menstruation, abortifacient, gout, fleas

hepatoxicity, nephrotoxicity, seizures

Pentagyn

Gynostemma pentaphyllum, Jiaogulan, miracle grass, Xianxio, Southern Ginseng

lower BP & cholesterol

increase warfarin effect, nausea, diarrhea

St. John's Wort

Hypericum perforatum, goat weed

mood disorders, depression

induces CYP3A4 & P-glycoprotein drug transporter, increased drug clearance, lower therapeutic drug levels

Saw Palmetto

Serenoa serrulata, Sabal serrulata, saw tooth palm

BPH, polycystic ovary syndrome, hirsutism

5-alpha reductase inhibition, testosterone metabolism inhibition

Skullcap

Scutellaria laterifolia, pimpernel, hoodwort, monkey flower, mad-dog weed, quaker bonnet

insomnia, irritability, nervousness, snakebites, rabies

hepatotoxic, giddiness, stupor, confusion, seizures

Valerian root

Valeriana officinalis, capon's tail

Insomnia, anxiety

neurotransmitter inhibition by enhancing GABA, tachycardia, hypotension, headache, delirium

Yohimbe

Corynanthe yohimbe, Pausinystalia yohimbine, yohimbehe, johimbe

aphrodesiac, impotence

Tachycardia, hypertension, urinary retention

 

Some herbs have structural similarity with digoxin and interfere with the digoxin immunoassay. Digoxin levels may be falsely elevated or decreased depending on the type of assay used in the laboratory. The herbal products that most often interfere with digoxin measurements are Chan Su, Dan Shen, Uzara root, Asian Ginseng and Siberian Ginseng. Fortunately, the Bayer Centaur assay used in the Saint Luke’s Health System is not adversely affected by these herbs.

Several herbal medicines lower the seizure threshold maintained by several anticonvulsants including phenobarbital and phenytoin. The most common offenders are Evening Primrose, Borage Oil and Shankhapushpi. Therapeutic drug levels may decrease up to 40% after ingestion of these products.

Many herbal medicines interact with warfarin and potentiate its anticoagulant effect, increasing the risk of bleeding. Some herbs can produce as much as a two-fold rise in INR. Examples include angelica root, arnica flower, ansine, bogbean, borage seed oil, Boldo-genugreek, capsicum, Dan Shen, Dong Quai, feverfew, garlic, ginger, Ginkgo biloba, licorice root and willow bark.

Other herbal medicines interfere with warfarin’s anticoagulant properties, leading to subtherapeutic INR values. In some cases, these herbs have been reported to decrease INR as much as 50%. The main culprits are ginseng, Saint John’s Wort and soy milk.

Some herbs can increase the risk of bleeding by inhibiting platelet aggregation. The best known examples are Dan Shen, garlic and Ginkgo biloba.

Besides interfering with warfarin, Saint John’s Wort has been reported to decrease the therapeutic concentration of several other medications. St. John’s wort induces the CPY3A4 mixed function oxidase, which is responsible for metabolism of 45% of CYP450 mediated drug metabolism. It also induces the P-glycoprotein drug transporter, reducing the efficacy of drugs in which hepatic metabolism is not the major pathway of clearance. Self medication with St. John’s wort can cause treatment failures due to an increase in the clearance of many prescribed medications. Examples include oral contraceptives, immuno-suppressants, HIV protease inhibitors, HIV non-nucleoside reverse transcriptase inhibitors, cardiac drugs and anti-neoplastic drugs such as irinotecan and imatinib mesylate. Specific examples include:

 

  • Lower concentrations in oral contraceptives may cause failed birth control.
  • A rapid and significant reduction in cyclosporine and tacrolimus concentrations in transplant patients may cause rejection.
  • A reduction in the AUC of indinavir by a mean of 57% and the trough level by 81%. Atazanavir lopinavir and ritonavir are similarly affected.
  • A decrease in the therapeutic level of theophylline requiring an increase in dosage from 300 mg bid to 800 mg bid.
  • Significantly decreased methadone levels, resulting in reappearance of withdrawal symptoms.
  • Significantly reduced levels of simvastatin, resulting in decreased cholesterol lowering effect. However, Pravastatin is not affected.
  • Decreased digoxin trough levels by 33% and peak levels by 26%.
  • Verapamil clearance is significantly increased.

 

Different brands of St. John’s wort may vary widely in the magnitude of these effects, because herbal supplements are not subject to rigorous pharmaceutical standards.

Some herbal medicines are hepatotoxic. Kava is the most notorious hepatotoxin and can produce a 70 fold increase in ALT and AST. Mistletoe berries have also been reported to elevate ALT and AST. Chaparral and germander have been associated with cholestatic hepatitis. Comfrey may cause hepatic veno-occlusive disease.

Kelp is promoted as a thyroid tonic and anti-inflammatory medicine. Kelp tablets contain substantial amounts of iodine, which can cause hyperthyroidism. T4 and T3 are increased, while TSH is suppressed.

Some herbal medicines affect glucose levels. Chromium is a trace metal that helps to regulate glucose metabolism. Athletes and bodybuilders take chromium supplements to enhance performance. Large doses can induce hyperglycemia. In contrast, ginseng has been associated with hypoglycemic episodes.

Licorice is used as an anti-inflammatory herb and as a remedy for peptic ulcers. Carbenoxolone, one of the components of licorice, can elevate blood pressure and cause hypokalemia. In extreme cases, licorice ingestion has been associated with hypokalemic myopathy. In these cases the mean plasma potassium level is 1.98 mEq/L and the mean CK level is 5300 IU/L.

Unexpected lead poisoning may occur from the use of herbal medicines contaminated with lead. Some Chinese herbs have been found to have lead content as high as 20,000 ppm. Ingestion of these products can lead to blood lead levels exceeding 100 ug/dL. Some patients may present with intoxication porphyria secondary to lead poisoning.

Because of these complications, the American Society of Anesthesiologists has suggested that in general patients should discontinue their herbal medicines at least 2 weeks before surgery. Other investigators have recommended that those herbal medicines that interfere with platelet function or coagulation should be discontinued at least 7 days prior to surgery.

In summary, herbal medicines should be considered whenever an otherwise healthy individual has an abnormal laboratory result. They should also be considered whenever a patient has an unexpected response to a prescribed medication or presents with unexplained organ toxicity.

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