Adrenal Tonic

Dosage for American Ginseng varies significantly based on the intended use and the concentration of bioactive ginsenosides. Because it is often sold as a non-standardized product, patients must pay close attention to the label and consult a healthcare provider.

• For Glycemic Control (Type 2 Diabetes): Clinical studies have utilized doses ranging from 200 mg to 3,000 mg per day. Often, a dose of 1,000 mg taken 40 minutes before a meal is used to mitigate post-meal blood sugar spikes.
• For Cognitive Function and Fatigue: Doses of 200 mg to 400 mg of a standardized extract (containing approximately 4-7% ginsenosides) are common. This is typically taken as a single dose in the morning or divided into two doses (morning and early afternoon).
• For Immune Support: During the cold and flu season, some providers suggest 200 mg twice daily for a period of 3 to 4 months to enhance immune resilience.

American Ginseng is not generally recommended for use in children under the age of 18. There is a lack of robust clinical data regarding the safety and long-term developmental effects of ginsenosides in the pediatric population. In rare cases where a pediatric allergist uses American Ginseng as an allergenic extract for testing, the dosage is strictly controlled and administered in a clinical setting. Do not administer American Ginseng supplements to children without direct medical supervision.

Renal Impairment

Patients with moderate to severe renal impairment (kidney disease) should exercise caution. Since metabolites are partially cleared through the kidneys, a reduction in dose or increased monitoring of blood pressure and glucose may be necessary. Specific GFR-based (Glomerular Filtration Rate) dosing has not been established, but starting at the lowest possible dose is advised.

Hepatic Impairment

Because the liver is involved in the metabolism of ginsenosides, patients with hepatic dysfunction (e.g., cirrhosis, hepatitis) may experience higher systemic levels of the compound. Close monitoring for side effects like insomnia or hypertension is required.

Elderly Patients

Geriatric patients (aged 65 and older) may be more sensitive to the effects of American Ginseng. There is an increased risk of interactions with other medications (polypharmacy) and a higher likelihood of underlying cardiovascular conditions. Lower starting doses (e.g., 100-200 mg) are recommended to assess tolerance.

• Timing: For blood sugar management, American Ginseng is most effective when taken 40 minutes before a meal. For general energy or cognitive support, it is best taken in the morning. Avoid taking it late in the evening, as it may interfere with sleep.
• Administration: Capsules and tablets should be swallowed whole with a full glass of water. If using the raw root for tea, it should be simmered (not boiled) for 15-20 minutes to extract the ginsenosides without degrading them.
• Consistency: The effects of American Ginseng may take several weeks to become fully apparent. It is often used in cycles (e.g., 8 weeks on, 2 weeks off) to prevent the development of tolerance or 'ginseng abuse syndrome.'
• Storage: Store in a cool, dry place away from direct sunlight. Keep out of reach of children and pets.

If you miss a dose, take it as soon as you remember. However, if it is nearly time for your next scheduled dose, skip the missed dose and return to your regular routine. Do not double the dose to make up for a missed one, as this increases the risk of side effects like heart palpitations or jitteriness.

Signs of an American Ginseng overdose (sometimes referred to as 'Ginseng Abuse Syndrome') may include:

• Severe insomnia and restlessness
• Significantly elevated blood pressure (hypertension)
• Rapid heart rate (tachycardia)
• Skin rashes or itching
• Diarrhea or vomiting
• Increased muscle tension

In the event of a suspected overdose, contact your local poison control center or seek emergency medical attention immediately. Emergency measures typically involve supportive care, such as intravenous fluids and medications to stabilize blood pressure or heart rhythm.

> Important: Follow your healthcare provider's dosing instructions. Do not adjust your dose without medical guidance, especially if you are taking medications for diabetes or high blood pressure.

While American Ginseng is generally well-tolerated when used appropriately, some individuals may experience mild to moderate side effects. The most frequently reported issues include:

• Insomnia: Due to its effects on the adrenergic system (Adrenergic Agonist [EPC]), many patients report difficulty falling or staying asleep, especially if the supplement is taken in the late afternoon or evening.
• Headache: A dull, aching sensation in the temples or forehead is common during the first few days of use as the body adjusts to the ginsenosides.
• Gastrointestinal Distress: This may manifest as mild nausea, abdominal cramping, or diarrhea. These symptoms are often transient and may be mitigated by taking the supplement with a small amount of food.
• Nervousness/Jitteriness: Similar to a caffeine-like effect, some users feel an increased sense of anxiety or physical restlessness.

• Blood Pressure Fluctuations: Some patients may experience a slight increase or decrease in blood pressure. Those with pre-existing hypertension should monitor their readings closely.
• Dizziness: A feeling of lightheadedness or vertigo may occur, particularly when standing up quickly.
• Breast Tenderness: In women, American Ginseng may exert mild estrogen-like effects, leading to mastalgia (breast pain) or menstrual irregularities.
• Vaginal Bleeding: Postmenopausal bleeding has been rarely reported and requires immediate medical evaluation.

• Severe Allergic Reactions: As a Non-Standardized Plant Allergenic Extract [EPC], American Ginseng can cause hypersensitivity reactions, including hives, swelling of the face or throat, and difficulty breathing.
• Stevens-Johnson Syndrome (SJS): There are extremely rare reports of severe skin reactions characterized by blistering and peeling of the skin and mucous membranes.
• Liver Enzyme Elevation: Rare cases of hepatotoxicity (liver damage) have been noted, typically in the context of multi-ingredient supplements.

> Warning: Stop taking American Ginseng and call your doctor immediately if you experience any of these serious symptoms:

• Hypoglycemia (Low Blood Sugar): Symptoms include sudden sweating, shaking, fast heartbeat, hunger, blurred vision, or confusion. This is particularly critical for diabetic patients.
• Anaphylaxis: A life-threatening allergic reaction involving swelling of the tongue, throat constriction, and a sharp drop in blood pressure.
• Severe Hypertension: A sudden, dangerous increase in blood pressure that may cause a severe headache, blurred vision, or nosebleed.
• Abnormal Heart Rhythms: Feeling like your heart is skipping beats, fluttering, or beating too hard (palpitations).
• Unusual Bleeding or Bruising: Because of its Anti-coagulant [EPC] properties, American Ginseng may increase the risk of bleeding from the nose or gums, or cause blood in the urine or stool.

Prolonged use of American Ginseng (beyond 3-6 months) without breaks may lead to Ginseng Abuse Syndrome. This condition is characterized by a combination of hypertension, nervousness, sleeplessness, skin eruptions, and morning diarrhea. Long-term use may also affect hormonal balance due to the interaction of ginsenosides with steroid hormone receptors, potentially leading to changes in libido or menstrual cycles.

No FDA black box warnings currently exist for American Ginseng. However, the FDA does require that allergenic extracts carry warnings regarding the risk of severe systemic reactions (anaphylaxis) when used for diagnostic testing or immunotherapy. For dietary supplement forms, the primary regulatory concern is the lack of standardization and the potential for contamination with other substances.

Report any unusual symptoms to your healthcare provider. Monitoring your body's response is essential, especially during the first two weeks of therapy.

American Ginseng is a potent pharmacological agent that can influence multiple organ systems. It is not 'just a herb' and must be treated with the same caution as any pharmaceutical drug. Patients with underlying medical conditions, particularly those involving the cardiovascular, endocrine, or immune systems, must consult a physician before use.

There are no FDA black box warnings for American Ginseng when used as a dietary supplement. However, as a Non-Standardized Food Allergenic Extract [EPC], healthcare providers are warned about the potential for life-threatening anaphylaxis during skin testing. Emergency equipment, including epinephrine, must be available when American Ginseng is administered in an allergenic extract capacity.

• Allergic Reactions / Anaphylaxis Risk: Individuals with known allergies to plants in the Araliaceae family (including English Ivy or Schefflera) are at a higher risk of cross-reactivity. If you experience itching, hives, or swelling, discontinue use immediately.
• Glycemic Instability: Because American Ginseng can lower blood sugar, it may potentiate the effects of insulin or oral hypoglycemic agents. This can lead to severe hypoglycemia, which is a medical emergency.
• Bleeding Risk: American Ginseng has Anti-coagulant [EPC] properties. It should be used with extreme caution in patients with bleeding disorders or those scheduled for surgery. Most surgeons recommend discontinuing American Ginseng at least 7 to 14 days prior to any surgical procedure to prevent excessive intraoperative bleeding.
• Hormone-Sensitive Conditions: Ginsenosides may act like estrogen in the body. If you have a condition that might be made worse by exposure to estrogen (such as breast cancer, uterine cancer, ovarian cancer, endometriosis, or uterine fibroids), do not use American Ginseng.
• Cardiovascular Risk: Due to its Adrenergic Agonist [EPC] profile, it may cause palpitations or blood pressure spikes in sensitive individuals or those with pre-existing heart disease.

If you are taking American Ginseng long-term, your healthcare provider may recommend the following monitoring:

• Blood Glucose Monitoring: Frequent checks of fasting and postprandial blood sugar levels, especially if you have diabetes.
• Blood Pressure Checks: Regular monitoring to ensure the supplement is not causing hypertension.
• Coagulation Studies: If you are taking blood thinners, your doctor may monitor your INR (International Normalized Ratio) or PT (Prothrombin Time) more closely.
• Liver Function Tests (LFTs): Periodic blood tests to ensure no hepatic irritation is occurring.

For most people, American Ginseng does not cause impairment. However, if you experience dizziness, nervousness, or blurred vision (a symptom of low blood sugar), you should avoid driving or operating heavy machinery until you know how the supplement affects you.

Alcohol may increase the sedative or stimulatory effects of American Ginseng unpredictably. Furthermore, alcohol can affect blood sugar levels, which may complicate the glycemic-modulating effects of the ginseng. It is generally advised to limit alcohol consumption while using this supplement.

Do not stop taking American Ginseng suddenly if you have been using it in high doses for a long period. While it does not have a traditional 'withdrawal syndrome,' sudden cessation may lead to a rebound effect in blood sugar or a temporary 'crash' in energy levels. Tapering the dose over one week is often recommended.

> Important: Discuss all your medical conditions with your healthcare provider before starting American Ginseng, particularly if you have diabetes, high blood pressure, or a history of hormone-sensitive cancers.

• Warfarin (Coumadin): American Ginseng may decrease the effectiveness of warfarin, increasing the risk of blood clots. This interaction is thought to occur through the induction of hepatic enzymes or by directly interfering with the drug's anticoagulant mechanism. Concurrent use is generally contraindicated unless under strict medical supervision with daily INR monitoring.
• MAO Inhibitors (MAOIs): Drugs such as phenelzine or tranylcypromine used for depression should not be combined with American Ginseng. This combination can lead to 'ginseng-MAOI' tremors, mania, or hypertensive crisis due to additive effects on the central nervous system and adrenergic receptors.

• Insulin and Oral Diabetes Medications: American Ginseng significantly enhances the blood-sugar-lowering effects of drugs like metformin, glipizide, and insulin. This increases the risk of severe hypoglycemia. Dosage adjustments of the diabetes medication are often required.
• Immunosuppressants: Because American Ginseng may stimulate the immune system, it can interfere with the efficacy of drugs used to prevent organ transplant rejection or treat autoimmune diseases (e.g., cyclosporine, tacrolimus, corticosteroids).
• Digoxin: There are reports that American Ginseng may falsely elevate digoxin level readings in lab tests or potentially increase the risk of digoxin toxicity.

• Antihypertensives: American Ginseng may counteract the effects of blood pressure medications like beta-blockers or ACE inhibitors due to its Adrenergic Agonist [EPC] properties.
• Estrogens: Taking American Ginseng along with birth control pills or hormone replacement therapy might increase the risk of estrogenic side effects like breast tenderness.
• Loop Diuretics (e.g., Furosemide): Ginseng may reduce the effectiveness of these 'water pills.'

• Caffeine: Combining American Ginseng with coffee, tea, or energy drinks can lead to excessive stimulation, rapid heart rate, and severe insomnia.
• High-Fat Meals: May delay the absorption of ginsenosides, reducing their peak concentration (Cmax) and delaying their onset of action.
• Grapefruit Juice: While not definitively proven, there is a theoretical risk that grapefruit juice could inhibit the metabolism of certain ginsenosides, leading to higher systemic levels.

• St. John's Wort: May induce enzymes that clear ginsenosides from the body more quickly, reducing their effectiveness.
• Bleeding-Risk Herbs: Combining American Ginseng with ginkgo biloba, garlic, ginger, or saw palmetto may further increase the risk of spontaneous bleeding.
• Bitter Orange/Ephedra: Combining with other adrenergic stimulants can lead to dangerous cardiovascular strain.

• Digoxin Assays: American Ginseng can interfere with certain immunoassays used to measure digoxin levels, leading to falsely high results.
• Blood Glucose Tests: May result in lower-than-expected readings, which must be interpreted in the context of the patient's overall clinical state.

For each major interaction, the mechanism often involves CYP3A4 induction or pharmacodynamic synergism (where two substances have similar effects that add together). The clinical consequence is typically either increased toxicity of the ginseng or reduced efficacy of the co-administered drug.

> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking. A complete medication review is the only way to prevent dangerous interactions.

American Ginseng must NEVER be used in the following circumstances:

1. 1Known Hypersensitivity: If you have had a previous allergic reaction to American Ginseng, Asian Ginseng, or any member of the Araliaceae plant family. The risk of anaphylaxis is high in these individuals.
2. 2Hormone-Sensitive Cancers: Because ginsenosides can exhibit estrogenic activity, American Ginseng is strictly contraindicated for individuals with active or a history of breast, uterine, or ovarian cancer.
3. 3Active Acute Infection: In Traditional Chinese Medicine and some clinical perspectives, ginseng is avoided during the 'acute phase' of an infection (like a high fever or pneumonia) as it may theoretically 'drive the pathogen deeper' or over-stimulate an already stressed immune system.
4. 4Organ Transplant Recipients: Due to its immune-stimulating properties, it may trigger graft-versus-host disease or organ rejection by counteracting immunosuppressive therapy.

Conditions requiring a careful risk-benefit analysis by a healthcare provider include:

• Schizophrenia or Bipolar Disorder: The stimulatory effects on the CNS may trigger manic episodes or worsen psychosis.
• Severe Hypertension: If blood pressure is not well-controlled by medication, the adrenergic effects of American Ginseng may cause a dangerous hypertensive crisis.
• Bleeding Disorders: Conditions like hemophilia or von Willebrand disease, where the Anti-coagulant [EPC] effects could be catastrophic.
• Planned Surgery: Must be stopped at least two weeks prior to any invasive procedure.

Patients should be aware of potential cross-sensitivity with:

• Ivy (Hedera helix): Often used in cough syrups.
• Asian Ginseng (Panax ginseng): While chemically different, they share many similar ginsenosides.
• Eleuthero (Siberian Ginseng): Though not a true ginseng, it is often processed in the same facilities and may cause similar reactions.

> Important: Your healthcare provider will evaluate your complete medical history, including any history of autoimmune disease or hormonal imbalances, before prescribing or recommending American Ginseng.

American Ginseng is likely unsafe during pregnancy.** It is categorized by some herbal safety references as Category B3 or C (meaning limited data but potential risk). Animal studies have shown that **Ginsenoside Rb1** is associated with teratogenic effects (birth defects), particularly heart and limb abnormalities, during early embryonic development. Furthermore, the hormonal effects of ginseng could potentially interfere with the delicate endocrine balance required to maintain a healthy pregnancy. **Pregnant women should avoid all forms of American Ginseng.

There is insufficient data to determine if ginsenosides pass into human breast milk. Because of the potential for American Ginseng to act as a stimulant and its estrogen-like effects, the risk to a nursing infant is unknown but potentially significant (e.g., irritability, sleep disturbances). It is generally recommended that breastfeeding mothers avoid use to ensure infant safety.

American Ginseng is not approved for use in children. Safety and efficacy have not been established. There are concerns that the hormonal and CNS-stimulating effects could interfere with normal growth and development. In cases of accidental ingestion by a child, monitor for extreme irritability, diarrhea, and rapid heart rate.

Elderly patients are at a higher risk for adverse effects from American Ginseng. Age-related declines in renal and hepatic clearance mean that standard doses may stay in the system longer. Furthermore, the elderly are more likely to be taking anticoagulants (like Eliquis or Xarelto) or heart medications, significantly increasing the risk of dangerous drug interactions. Geriatric patients should always start with a very low dose (e.g., 100 mg) and have their blood pressure monitored weekly.

In patients with a GFR below 30 mL/min, the excretion of ginsenoside metabolites is significantly slowed. This can lead to an accumulation of the drug, increasing the risk of 'Ginseng Abuse Syndrome.' While no specific dose-reduction formula exists, a 50% reduction in the standard dose is often suggested for those with Stage 4 or 5 Chronic Kidney Disease (CKD).

Patients with Child-Pugh Class B or C hepatic impairment should avoid American Ginseng. The liver's reduced ability to process triterpene saponins can lead to unpredictable blood levels and potential hepatotoxicity. If use is deemed necessary, liver enzymes (ALT, AST) should be checked every 4 weeks.

> Important: Special populations require individualized medical assessment. Never start a botanical regimen in these groups without consulting a specialist in maternal-fetal medicine, pediatrics, or geriatrics.

American Ginseng (Panax quinquefolius) exerts its effects through a multi-targeted approach. The primary active constituents, ginsenosides, are divided into two main groups: protopanaxadiols (e.g., Rb1, Rc, Rd) and protopanaxatriols (e.g., Re, Rf, Rg1).

1. 1Adrenergic Modulation: It acts as an Adrenergic alpha-Agonist [MoA] and Adrenergic beta-Agonist [MoA], influencing the release and uptake of catecholamines. This modulates the 'fight or flight' response, providing an adaptogenic effect that helps the body resist stress.
2. 2Glycemic Regulation: Ginsenosides increase insulin secretion from the pancreas, enhance insulin sensitivity in peripheral tissues, and regulate glucose uptake in the liver by modulating the AMPK pathway.
3. 3Calcium Chelation: Through its Calcium Chelating Activity [MoA], it can influence voltage-gated calcium channels, which has implications for neuroprotection and muscle relaxation.
4. 4Anti-coagulation: It inhibits platelet aggregation, acting as an Anti-coagulant [EPC], likely by interfering with thromboxane A2 signaling.

• Onset of Action: For glycemic effects, the onset is approximately 30 to 60 minutes post-ingestion. For cognitive and adaptogenic effects, several days to weeks of consistent use may be required.
• Duration of Effect: The acute glucose-lowering effect lasts for approximately 2 to 4 hours. CNS effects may persist for 8 to 12 hours.
• Tolerance: Long-term use can lead to a downregulation of receptors, meaning higher doses may be needed to achieve the same effect. This is why 'cycling' the supplement is recommended.

| Parameter | Value |

|---|---|

| Bioavailability | < 5% (Oral) |

| Protein Binding | 70% - 90% (Albumin) |

| Half-life | 2 - 18 hours (Variable by ginsenoside) |

| Tmax | 1.5 - 2.5 hours |

| Metabolism | Hepatic (CYP3A4, CYP2C9) and Intestinal Microbiota |

| Excretion | Renal 20%, Fecal 80% |

• Molecular Formula: C42H72O13 (for Ginsenoside Rb1)
• Molecular Weight: 1109.3 g/mol (Rb1)
• Solubility: Sparingly soluble in water; highly soluble in ethanol and methanol.
• Structure: A steroid-like dammarane skeleton with various sugar moieties attached at the C-3 and C-20 positions.

American Ginseng is classified as a Non-Standardized Food Allergenic Extract [EPC]. It is related to other adaptogens like Asian Ginseng and Ashwagandha, but its specific regulatory classification as an allergenic extract places it in a unique category of diagnostic and therapeutic agents.