Angelica Sinensis Root

Dosage for Angelica Sinensis Root is not standardized by the FDA, and clinical recommendations vary based on the form used and the condition being addressed. In traditional clinical practice, the following ranges are often observed:

• Dried Root Decoction: 3 to 15 grams of the dried root simmered in water daily, typically divided into three doses.
• Powdered Root Capsules: 500 mg to 2,000 mg taken two to three times daily.
• Liquid Extract (1:2 ratio): 2 mL to 5 mL taken three times daily.

For its use as an Allergenic Extract, the dosage is highly individualized and determined by an allergist using standardized titration protocols to ensure patient safety during immunotherapy or diagnostic testing.

Angelica Sinensis Root is generally not recommended for pediatric use. There is a lack of robust clinical data regarding its safety and efficacy in children. Because of its potent effects on the endocrine system (Estrogen Receptor Agonist properties), there is a theoretical risk that it could interfere with normal hormonal development or puberty. Healthcare providers typically advise against its use in patients under the age of 18 unless specifically directed by a specialist in pediatric allergy or endocrinology.

Renal Impairment

There are no established guidelines for dosage adjustment in patients with renal impairment. However, because the metabolites of Angelica Sinensis Root are primarily excreted through the kidneys, patients with a GFR (Glomerular Filtration Rate) below 60 mL/min should use this substance with extreme caution. Your doctor may recommend a lower starting dose to prevent accumulation and potential toxicity.

Hepatic Impairment

As the liver is the primary site for the metabolism of coumarins and ferulic acid found in the root, patients with hepatic impairment (Child-Pugh Class B or C) are at an increased risk for adverse effects. Reduced clearance can lead to higher systemic levels of coumarin-like derivatives, increasing the risk of hepatotoxicity or coagulopathy. Close monitoring of liver function tests (LFTs) is required.

Elderly Patients

Geriatric patients should begin at the lowest end of the dosing spectrum. This population is more susceptible to the vasodilatory effects (risk of orthostatic hypotension) and the potential for drug-drug interactions due to polypharmacy. Renal function should be assessed before initiating use in the elderly.

• With or Without Food: It is generally recommended to take oral forms with food to minimize gastrointestinal upset, which is a common side effect.
• Consistency: To maintain stable systemic levels of its phytoestrogens, the doses should be spaced evenly throughout the day.
• Form Integrity: Capsules should be swallowed whole. If using a decoction, the root should be strained out before consumption.
• Storage: Store all forms in a cool, dry place away from direct sunlight. The active volatile oils (like ligustilide) are sensitive to heat and light and can degrade over time, reducing the product's potency.

If you miss a dose of Angelica Sinensis Root, take it as soon as you remember. However, if it is almost time for your next scheduled dose, skip the missed dose and resume your regular schedule. Do not double the dose to catch up, as this increases the risk of side effects, particularly gastrointestinal distress and potential bleeding issues.

Symptoms of an overdose of Angelica Sinensis Root may include severe nausea, vomiting, extreme photosensitivity (skin redness or blistering upon sun exposure), and excessive bleeding or bruising. In cases of significant ingestion, central nervous system depression or arrhythmias may occur due to the high concentration of volatile oils.

Emergency Measures: If an overdose is suspected, contact a poison control center immediately or seek emergency medical attention. Treatment is primarily supportive, focusing on maintaining airway patency, monitoring cardiovascular status, and managing any acute bleeding episodes.

> Important: Follow your healthcare provider's dosing instructions strictly. Do not adjust your dose or switch between different brands/forms without medical guidance, as potency varies significantly.

The most frequently reported side effects associated with Angelica Sinensis Root involve the gastrointestinal system and the skin. Patients often experience:

• Gastrointestinal Upset: This includes nausea, bloating, and mild diarrhea. It typically occurs shortly after ingestion and may diminish as the body adjusts to the supplement.
• Photosensitivity: Due to the presence of psoralens (furocoumarins), the skin becomes significantly more sensitive to ultraviolet (UV) radiation. Patients may find they sunburn much more easily than usual, even with minimal exposure.
• Abdominal Cramping: While used to treat cramps, some patients report a paradoxical increase in mild uterine or intestinal cramping during the first few days of use.

• Dizziness and Lightheadedness: Attributed to the drug's role as a Nitrate Vasodilator [EPC], which can cause a slight drop in blood pressure.
• Headache: Some patients report dull, persistent headaches, possibly related to changes in vascular tone.
• Drowsiness: A mild sedative effect has been noted in some clinical observations, particularly with high-dose liquid extracts.
• Increased Menstrual Flow: Women may notice their menstrual period is heavier or lasts longer (menorrhagia) due to the herb's anti-platelet and vasodilatory properties.

• Hepatotoxicity: Rare cases of elevated liver enzymes have been reported, particularly when used in combination with other herbs.
• Gynaecomastia: In male patients, the Estrogen Receptor Agonist activity may lead to the development of breast tissue.
• Severe Dermatitis: Beyond simple photosensitivity, some individuals may develop a full-blown phytophotodermatitis, characterized by blistering and hyperpigmentation.

> Warning: Stop taking Angelica Sinensis Root and call your doctor immediately if you experience any of these serious symptoms.

• Anaphylaxis / Severe Allergic Reaction: Symptoms include swelling of the face, lips, or tongue; difficulty breathing; and a rapid, weak pulse. As a Non-Standardized Plant Allergenic Extract, the risk of Type I hypersensitivity is significant in predisposed individuals.
• Uncontrolled Bleeding: This includes persistent nosebleeds, blood in the urine or stool (black, tarry stools), or coughing up blood. The coumarin content can interfere with blood clotting.
• Severe Hypotension: Fainting, extreme weakness, or a feeling that you might pass out, indicating a dangerous drop in blood pressure.
• Jaundice: Yellowing of the eyes or skin, which may indicate acute liver injury.

Prolonged use of Angelica Sinensis Root (longer than 6 months) has not been well-studied. Potential long-term risks include:

• Hormone-Sensitive Tissue Changes: Due to its Estrogen Receptor Agonist [MoA] properties, there is a theoretical concern that long-term use could stimulate the growth of estrogen-dependent tissues, potentially increasing the risk of endometrial hyperplasia.
• Chronic Photosensitivity: Long-term exposure to psoralens without adequate UV protection may increase the risk of premature skin aging and skin malignancies.
• Coagulation Issues: Chronic inhibition of platelet aggregation may lead to an increased risk of internal bleeding over time.

No FDA black box warnings for Angelica Sinensis Root. However, healthcare providers emphasize that the lack of a black box warning does not imply absolute safety, particularly regarding its interactions with anticoagulants and its effects on hormone-sensitive cancers.

Report any unusual symptoms or changes in your health to your healthcare provider promptly. Clinical monitoring of prothrombin time (PT/INR) may be necessary if you are also taking blood-thinning medications.

Angelica Sinensis Root is a potent pharmacological agent that affects multiple systems, including the blood, the heart, and the endocrine system. It is not a 'simple' herbal tea; it contains active coumarin derivatives and phytoestrogens that can significantly alter the efficacy of prescription medications. Patients must be aware that botanical products are not subject to the same rigorous pre-market testing as synthetic drugs, and 'natural' does not equate to 'safe.'

Currently, there are no FDA black box warnings for Angelica Sinensis Root. It is regulated as a dietary supplement for most uses and as an allergenic extract for diagnostic purposes. However, clinical literature strongly warns against its use in patients with active bleeding disorders or those scheduled for surgery.

• Allergic Reactions / Anaphylaxis Risk: As a member of the Apiaceae family (which includes celery, carrots, and parsley), cross-reactivity is common. If you have known allergies to these foods, you are at a high risk for a severe allergic reaction to Angelica Sinensis Root.
• Bleeding Risk: The herb contains coumarin-like constituents that have anti-platelet and mild anticoagulant effects. It should be used with extreme caution in patients with hemophilia, von Willebrand disease, or those taking anticoagulants like warfarin.
• Hormone-Sensitive Conditions: Because it acts as an Estrogen Receptor Agonist [MoA], it may worsen conditions such as breast cancer, uterine cancer, ovarian cancer, endometriosis, or uterine fibroids. If you have any condition that could be made worse by exposure to estrogen, avoid this product.
• Photosensitivity: You must avoid prolonged sun exposure and tanning beds while taking this medication. Use high-SPF sunscreen and wear protective clothing to prevent severe burns.
• Surgery: Due to the risk of excessive bleeding, Angelica Sinensis Root must be discontinued at least 14 days prior to any elective surgical or dental procedure.

Patients taking Angelica Sinensis Root long-term or in high doses may require the following monitoring:

• Prothrombin Time (PT) and International Normalized Ratio (INR): To ensure blood is clotting correctly, especially if the patient is on other medications that affect coagulation.
• Liver Function Tests (LFTs): To monitor for potential hepatotoxicity.
• Dermatological Exams: Periodic skin checks for patients with high UV exposure.
• Endometrial Monitoring: For post-menopausal women, a doctor may recommend periodic ultrasounds to ensure the estrogenic effects are not causing abnormal thickening of the uterine lining.

Angelica Sinensis Root may cause dizziness or drowsiness in some individuals, particularly when first starting the treatment or when taking liquid extracts. Do not drive, operate heavy machinery, or engage in hazardous activities until you know how this substance affects you.

Alcohol should be avoided or strictly limited. Alcohol can increase the sedative effects of the herb and may also increase the risk of gastrointestinal irritation. Furthermore, both alcohol and Angelica Sinensis Root are processed by the liver; combined use may increase the metabolic burden on hepatic enzymes.

There is no evidence of a specific withdrawal syndrome; however, it is generally advised to taper the dose over one week rather than stopping abruptly, especially if it was being used to manage vasomotor symptoms (hot flashes), as a sudden drop in phytoestrogen levels may cause a rebound effect.

> Important: Discuss all your medical conditions, including any history of cancer or bleeding disorders, with your healthcare provider before starting Angelica Sinensis Root.

• Warfarin (Coumadin): Angelica Sinensis Root must NEVER be used with warfarin. The herb contains coumarin derivatives that can synergistically enhance the anticoagulant effect of warfarin, leading to dangerously high INR levels and life-threatening internal bleeding.
• Tamoxifen: Since Angelica Sinensis Root acts as an Estrogen Receptor Agonist [MoA], it may interfere with the estrogen-blocking effects of tamoxifen used in breast cancer treatment, potentially reducing the efficacy of the cancer therapy.

• Antiplatelet Drugs (Clopidogrel, Ticagrelor): Combined use increases the risk of bruising and bleeding because both the drug and the herb inhibit platelet aggregation.
• NSAIDs (Aspirin, Ibuprofen, Naproxen): Chronic use of NSAIDs with Angelica Sinensis Root significantly increases the risk of gastrointestinal bleeding and ulceration.
• Low Molecular Weight Heparins (Enoxaparin): Increased risk of hematoma and systemic bleeding.

• Oral Contraceptives and Hormone Replacement Therapy (HRT): The phytoestrogens in the root may compete for receptor sites or add to the total estrogenic load, potentially increasing side effects like breast tenderness or nausea, or altering the efficacy of the birth control.
• Antihypertensive Drugs: As a Nitrate Vasodilator [EPC], Angelica Sinensis Root may enhance the effects of blood pressure medications (e.g., Amlodipine, Lisinopril), leading to hypotension (excessively low blood pressure).
• Cytochrome P450 3A4 Substrates: The herb may inhibit or induce CYP3A4, changing the blood levels of medications like certain statins, calcium channel blockers, and benzodiazepines.

• Grapefruit Juice: Grapefruit inhibits CYP3A4, which is involved in the metabolism of several compounds in Angelica Sinensis Root. This can lead to increased systemic levels of the herb's active markers and a higher risk of toxicity.
• High-Fat Meals: May increase the absorption of lipophilic components like ligustilide, potentially increasing the intensity of side effects.

• St. John's Wort: Both substances cause photosensitivity. Taking them together significantly increases the risk of severe sunburn and skin damage.
• Anticoagulant Herbs: Ginkgo biloba, Garlic, Ginger, and Feverfew all have blood-thinning properties. Combining these with Angelica Sinensis Root creates a cumulative risk for hemorrhage.
• Phytoestrogen Herbs: Soy, Red Clover, and Black Cohosh may have additive effects on the hormonal system, which could lead to unpredictable changes in hormone-sensitive conditions.

• Prothrombin Time (PT/INR): Angelica Sinensis Root can cause a false or actual elevation in INR results.
• Estradiol Assays: The phytoestrogens may cross-react with certain immunoassays for estradiol, leading to inaccurate laboratory reports of a patient's natural estrogen levels.

For each interaction, the clinical consequence is typically an increased risk of toxicity (bleeding or hypotension) or a reduction in the efficacy of hormonal therapies. Management strategies usually involve avoiding the combination or performing frequent laboratory monitoring.

> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking, including those used occasionally like aspirin.

Angelica Sinensis Root must NEVER be used in the following circumstances:

1. 1Active Major Bleeding: Patients with peptic ulcers, intracranial hemorrhage, or other active bleeding sites. The herb's anti-platelet and vasodilatory effects will exacerbate blood loss.
2. 2Pregnancy: It is strictly contraindicated during pregnancy. It is known to have uterine stimulant effects (oxytocic activity) which can lead to miscarriage or premature labor.
3. 3Hormone-Sensitive Cancers: Patients with a history of or active breast, uterine, or ovarian cancer. The Estrogen Receptor Agonist [MoA] activity may stimulate the proliferation of malignant cells.
4. 4Pre-operative Period: Must not be used within 14 days of surgery due to the risk of perioperative hemorrhage.
5. 5Hypersensitivity: Known severe allergy to any plant in the Apiaceae family.

Conditions requiring a careful risk-benefit analysis by a physician include:

• Endometriosis and Uterine Fibroids: While sometimes used for these conditions in TCM, the estrogenic activity could theoretically cause these tissues to grow or become more symptomatic.
• Chronic Diarrhea or Abdominal Bloating: In TCM theory, this herb is 'cloying' and can worsen 'damp' conditions of the digestive tract.
• Protein S or Protein C Deficiency: Patients with underlying hypercoagulable states who are on anticoagulation; the unpredictable effect of the herb on the clotting cascade makes it dangerous.

Patients should be aware of potential cross-sensitivity. If you have had an allergic reaction (rash, hives, or breathing trouble) to the following, you should avoid Angelica Sinensis Root:

• Celery
• Carrots
• Parsley
• Dill
• Anise
• Fennel
• Coriander/Cilantro

> Important: Your healthcare provider will evaluate your complete medical history and current medication list before determining if Angelica Sinensis Root is safe for you.

FDA Pregnancy Category: Not Assigned (Contraindicated). Angelica Sinensis Root is considered unsafe for use during pregnancy. Clinical and pharmacological data indicate that the herb contains compounds that stimulate uterine contractions. In traditional medicine, it has been used as an abortifacient. There is also a risk of teratogenicity (birth defects) due to the potential for hormonal disruption during critical stages of fetal development. If you become pregnant while taking this herb, discontinue use immediately and consult your obstetrician.

It is not known whether the active constituents of Angelica Sinensis Root pass into human breast milk. However, due to the potential for hormonal effects (Estrogen Receptor Agonist activity) on the nursing infant and the risk of photosensitivity, its use is not recommended while breastfeeding. Healthcare providers generally advise nursing mothers to avoid botanical supplements with known hormonal activity to ensure infant safety.

Angelica Sinensis Root is not approved for use in children. The primary concern is the potential for the herb's phytoestrogens to interfere with the delicate hypothalamic-pituitary-gonadal axis during growth. This could theoretically lead to precocious puberty or other developmental issues. Its use as an Allergenic Extract in children should only be conducted by a board-certified allergist.

Elderly patients (65 years and older) are at an increased risk for adverse effects from Angelica Sinensis Root. The Nitrate Vasodilator [EPC] effects can lead to orthostatic hypotension, increasing the risk of falls and subsequent fractures. Furthermore, age-related declines in renal and hepatic clearance can lead to the accumulation of coumarin metabolites. Geriatric patients are also more likely to be taking interacting medications like aspirin or blood pressure drugs, making polypharmacy a major concern.

There is limited data on the use of Angelica Sinensis Root in patients with kidney disease. Because the metabolites are renally excreted, patients with a creatinine clearance (CrCl) of less than 30 mL/min should avoid use. For those with mild-to-moderate impairment, frequent monitoring of electrolytes and blood pressure is suggested if the herb is used.

Use with extreme caution in patients with liver disease. The liver is responsible for detoxifying the coumarins found in the root. In patients with cirrhosis or hepatitis, the half-life of these compounds is significantly extended, which can lead to toxicity and an increased risk of bleeding. This herb should be avoided in patients with Child-Pugh Class C hepatic impairment.

> Important: Special populations require individualized medical assessment. Never start a new supplement regimen without consulting a specialist who understands your specific health profile.

Angelica Sinensis Root exerts its effects through several distinct molecular pathways:

1. 1Estrogen Receptor Modulation: Phytoestrogens such as β-sitosterol and flavonoids bind to ER-α and ER-β. In environments with low endogenous estrogen (like menopause), they act as weak agonists. In high-estrogen environments, they may competitively inhibit more potent endogenous estrogens.
2. 2Nitric Oxide Pathway: Ferulic acid stimulates the endothelial nitric oxide synthase (eNOS) enzyme, increasing the production of nitric oxide (NO). NO diffuses into vascular smooth muscle, activating guanylyl cyclase and increasing cGMP, which leads to vasodilation.
3. 3Anti-platelet Activity: Certain coumarins and ferulic acid inhibit the release of serotonin from platelets and interfere with thromboxane A2 (TXA2) synthesis, thereby reducing platelet aggregation.
4. 4Immunomodulation: Polysaccharides in the root have been shown to stimulate the production of Interferon gamma [EPC] and other cytokines, potentially modulating the Th1/Th2 immune balance.

The onset of the vasodilatory effect is relatively rapid (within 1-2 hours), while the hormonal modulating effects may take several weeks of consistent use to become apparent. Tolerance to the vasodilatory effects can develop with chronic use, similar to other nitrate-containing compounds.

| Parameter | Value |

|---|---|

| Bioavailability | 50% - 70% (Ferulic acid) |

| Protein Binding | 80% - 95% (Coumarins) |

| Half-life | 1.5 - 4 hours (Ligustilide) |

| Tmax | 1 - 2 hours |

| Metabolism | Hepatic (CYP3A4, CYP2C9) |

| Excretion | Renal (80%), Fecal (15%) |

• Molecular Components: Contains volatile oils (0.4%–0.7%) dominated by ligustilide; organic acids (ferulic acid); coumarins (psoralen, bergapten); and polysaccharides.
• Solubility: Lipophilic components (ligustilide) are soluble in ethanol; hydrophilic components (polysaccharides, ferulic acid) are soluble in water.
• Structural Description: A complex botanical matrix; the primary active marker ligustilide is a phthalide derivative with the formula C12H14O2.

Angelica Sinensis Root is classified as a Non-Standardized Plant Allergenic Extract [EPC] and a Nitrate Vasodilator [EPC]. Within the realm of botanical medicine, it is considered a phytoestrogen and a blood-tonifying agent. It is pharmacologically related to other Apiaceae plants but is unique in its high concentration of phthalides.