Cinnamon

The dosage of Cinnamon varies significantly depending on the intended use and the specific variety of the plant being utilized.

• For Glycemic Support (Investigational): Clinical trials have utilized doses ranging from 500 mg to 2,000 mg (2 grams) of powdered cinnamon per day, typically divided into two or three doses. If using a concentrated aqueous extract, the dose is often lower, ranging from 112 mg to 250 mg twice daily.
• For Allergy Testing: The dosage is determined by the allergist and involves minute quantities (drops) of a non-standardized extract applied topically during a skin prick test.
• For Lipid Management: Doses similar to those used for glycemic support (1-2 grams daily) have been studied.

Cinnamon is not FDA-approved for any specific therapeutic indication in children. While dietary intake is generally considered safe, medicinal supplementation in the pediatric population is not well-studied.

• General Guidance: Most healthcare providers advise against high-dose cinnamon supplements in children under the age of 12 due to the lack of safety data and the potential for hepatotoxicity from coumarin.
• Allergy Testing: Pediatric use for diagnostic purposes must be performed by a board-certified allergist in a controlled clinical setting.

Renal Impairment

There are no specific dosage adjustments provided for patients with renal impairment; however, since metabolites are primarily excreted renally, caution is advised. Patients with end-stage renal disease (ESRD) should consult their nephrologist before initiating high-dose supplementation.

Hepatic Impairment

Significant caution is required. Cassia cinnamon contains coumarin, which is hepatotoxic. Patients with pre-existing liver disease (e.g., cirrhosis, hepatitis) should avoid Cassia cinnamon and may need to limit Ceylon cinnamon to culinary amounts. Dosage adjustments are not established, but avoidance is generally recommended in moderate to severe hepatic impairment.

Elderly Patients

Elderly patients may be more sensitive to the anticoagulant effects of coumarin or the hypoglycemic effects of cinnamon. It is recommended to start at the lowest possible dose and monitor liver enzymes and blood glucose closely.

1. 1With Food: It is generally recommended to take cinnamon supplements with meals to reduce the risk of gastrointestinal upset and to maximize the effect on post-prandial (after-meal) blood glucose levels.
2. 2Consistency: For metabolic benefits, cinnamon should be taken at the same time each day to maintain steady-state levels of bioactive compounds.
3. 3Swallowing: Capsules and tablets should be swallowed whole with a full glass of water. Do not attempt to swallow dry cinnamon powder (the "cinnamon challenge"), as this poses a severe risk of aspiration pneumonia and lung damage.
4. 4Storage: Store cinnamon supplements in a cool, dry place away from direct sunlight. The volatile oils (cinnamaldehyde) can degrade when exposed to heat or light, reducing the potency of the product.

If you miss a dose of Cinnamon, take it as soon as you remember. 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 hypoglycemia or liver irritation.

Signs of a Cinnamon overdose may include:

• Severe skin irritation or mouth sores
• Rapid heart rate (tachycardia)
• Dizziness or fainting (due to hypoglycemia)
• Nausea, vomiting, and upper abdominal pain (suggestive of liver stress)
• Shortness of breath

In the event of a suspected overdose, especially involving concentrated cinnamon oil or large quantities of Cassia powder, contact your local poison control center or seek emergency medical attention immediately.

> Important: Follow your healthcare provider's dosing instructions. Do not adjust your dose without medical guidance.

While Cinnamon is generally recognized as safe (GRAS) when used in culinary amounts, its use as a concentrated therapeutic agent or allergenic extract can lead to various side effects. The severity and frequency of these effects often depend on the variety of cinnamon (Cassia vs. Ceylon) and the route of administration.

• Gastrointestinal Upset: Many patients report mild stomach discomfort, gas, or bloating when starting cinnamon supplements. This is typically transient and improves as the body adjusts.
• Contact Stomatitis: Frequent consumption of cinnamon-flavored products or supplements can cause irritation of the oral mucosa. This feels like a burning sensation in the mouth, often accompanied by redness or small white patches.
• Skin Irritation: When used topically or during allergy testing, redness and itching at the site of contact are very common, especially in individuals with sensitive skin.

• Hypoglycemia: In patients already taking diabetes medications, cinnamon may lower blood sugar too much. Symptoms include shakiness, sweating, confusion, and palpitations.
• Diarrhea: High doses of cinnamon can irritate the lining of the intestines, leading to loose stools.
• Dizziness: Some users report a feeling of lightheadedness, which may be related to changes in blood pressure or glucose levels.

• Hepatotoxicity: This is the most concerning rare side effect, primarily associated with Cassia cinnamon. Coumarin can cause inflammation of the liver, leading to elevated liver enzymes. In rare cases, this can progress to clinical hepatitis or liver failure.
• Severe Allergic Reactions (Anaphylaxis): Although rare, some individuals may experience a systemic allergic reaction characterized by hives, swelling of the face or throat, and difficulty breathing.
• Photosensitivity: Some compounds in cinnamon may make the skin more sensitive to sunlight, increasing the risk of sunburn.

> Warning: Stop taking Cinnamon and call your doctor immediately if you experience any of these.

• Jaundice: Yellowing of the eyes or skin, which is a hallmark sign of liver dysfunction.
• Dark Urine: Often an early indicator of liver stress or rhabdomyolysis (though the latter is extremely rare with cinnamon).
• Persistent Abdominal Pain: Specifically in the upper right quadrant, which may indicate liver inflammation.
• Severe Skin Rash: A widespread, blistering, or peeling rash could indicate a severe hypersensitivity reaction.
• Extreme Hypoglycemia: If you become unresponsive or have a seizure due to low blood sugar.

• Liver Enzyme Elevation: Chronic use of high-dose Cassia cinnamon can lead to persistent elevations in ALT and AST levels. This usually reverses upon discontinuation but requires monitoring.
• Cumulative Anticoagulation: Long-term intake of coumarin-containing cinnamon may slightly increase the risk of bruising or bleeding, especially if combined with other blood thinners.
• DNA Damage (Theoretical): High doses of coumarin have shown genotoxic potential in animal models, though the relevance to human dietary intake is debated.

There are currently no FDA-mandated Black Box Warnings for Cinnamon allergenic extracts or supplements. However, clinical guidelines emphasize the risk of liver injury associated with coumarin-rich varieties.

Report any unusual symptoms to your healthcare provider. Monitoring of liver function is recommended for anyone using high-dose cinnamon supplements for more than 4-6 weeks.

Cinnamon is a potent biological agent and should not be viewed merely as a harmless spice when used in medicinal quantities. The most critical safety consideration is the distinction between Ceylon cinnamon (Cinnamomum verum) and Cassia cinnamon (Cinnamomum cassia). Cassia contains significantly higher levels of coumarin, a compound known to cause liver damage in sensitive individuals.

No FDA black box warnings for Cinnamon. However, it is regulated strictly as an allergenic extract when used for diagnostic purposes to prevent accidental systemic exposure in highly sensitized patients.

Allergic Reactions / Anaphylaxis Risk

Individuals with a known allergy to Balsam of Peru may have a cross-sensitivity to Cinnamon. Exposure can lead to contact dermatitis, oral stomatitis, or in severe cases, systemic anaphylaxis. Healthcare providers should perform a thorough allergy history before using cinnamon extracts.

Hepatotoxicity (Liver Toxicity)

Due to the coumarin content in Cassia cinnamon, there is a risk of liver injury. This risk is dose-dependent and may be exacerbated in individuals with pre-existing liver conditions or those taking other hepatotoxic medications (e.g., acetaminophen, statins). If you have a history of liver disease, discuss this with your doctor before using cinnamon supplements.

Hypoglycemia (Low Blood Sugar)

Cinnamon has potent insulin-sensitizing effects. While beneficial for many, it can cause dangerously low blood sugar levels in patients taking insulin or oral hypoglycemic agents like sulfonylureas. Frequent blood glucose monitoring is required when initiating cinnamon therapy.

Surgery

Because of its potential anticoagulant properties and its effect on blood sugar, Cinnamon should be discontinued at least two weeks prior to elective surgery. Failure to do so may increase the risk of intraoperative bleeding or difficulty managing blood glucose levels during and after the procedure.

If you are taking Cinnamon supplements for a chronic condition, your healthcare provider may require the following tests:

• Liver Function Tests (LFTs): To monitor for elevations in ALT, AST, and bilirubin, particularly if using Cassia cinnamon.
• Hemoglobin A1c and Fasting Glucose: To assess the efficacy of the supplement and ensure blood sugar does not drop too low.
• Prothrombin Time (PT/INR): In rare cases where high doses are combined with other anticoagulants.

Cinnamon itself does not typically cause sedation. However, if you experience hypoglycemia (dizziness, blurred vision, shakiness) as a result of taking cinnamon with diabetes medications, your ability to drive or operate heavy machinery may be impaired. Do not engage in these activities until you know how cinnamon affects your blood sugar.

Alcohol should be consumed with extreme caution. Both alcohol and coumarin (in Cassia cinnamon) are processed by the liver. Combining them can increase the metabolic strain on the liver and heighten the risk of hepatotoxicity. Furthermore, alcohol can mask the symptoms of hypoglycemia.

There is no known withdrawal syndrome associated with Cinnamon. However, if you are using it to manage blood sugar, stopping it suddenly may lead to a spike in glucose levels (rebound hyperglycemia). Always consult your doctor before discontinuing a supplement used for a chronic medical condition.

> Important: Discuss all your medical conditions with your healthcare provider before starting Cinnamon.

• Hepatotoxic Drugs (High-Dose): Combining high-dose Cassia cinnamon with medications known to cause liver injury, such as Leflunomide or Teriflunomide, is contraindicated due to the additive risk of severe hepatic necrosis.
• Specific Anticoagulants: While not an absolute contraindication for culinary use, therapeutic doses of cinnamon should not be used with Warfarin without strict medical supervision, as the coumarin in cinnamon can potentiate the anticoagulant effect, leading to life-threatening hemorrhage.

• Diabetes Medications: Cinnamon interacts significantly with Insulin, Metformin, Glyburide, and Pioglitazone. The mechanism is a synergistic pharmacodynamic interaction where both substances lower blood glucose. The clinical consequence is an increased risk of severe hypoglycemia. Management involves frequent glucose monitoring and potential downward titration of the pharmaceutical medication.
• Hepatotoxic Agents: Medications like Acetaminophen (Tylenol), Amiodarone, and Methotrexate can have their liver-damaging potential increased when taken with Cassia cinnamon.

• Statins: Drugs like Atorvastatin and Simvastatin are processed by the liver. Since cinnamon can also affect liver enzymes, there is a moderate risk of increased side effects from the statins, including myopathy.
• Cytochrome P450 2A6 (CYP2A6) Substrates: Coumarin is a substrate for CYP2A6. Cinnamon may compete for this enzyme, potentially increasing the plasma levels of other drugs metabolized by this pathway.

• High-Fat Meals: May increase the absorption of lipid-soluble components of cinnamon, potentially increasing the risk of side effects.
• Alcohol: As noted previously, alcohol increases the risk of liver toxicity and can complicate blood sugar management.
• Garlic and Ginger: These supplements also have mild anticoagulant properties. Combining them with high-dose cinnamon may further increase the risk of bruising or bleeding.

• Alpha-Lipoic Acid / Chromium: These supplements also lower blood sugar. Combining them with cinnamon significantly increases the risk of hypoglycemia.
• Red Yeast Rice: Often used for cholesterol, this can be hard on the liver. Combining it with Cassia cinnamon increases the risk of hepatic strain.
• St. John's Wort: May induce liver enzymes that change the rate at which cinnamon's bioactive compounds are metabolized.

• Liver Function Tests: Cinnamon can cause false elevations or clinically significant increases in ALT, AST, and Bilirubin.
• Blood Glucose Tests: May show lower-than-expected results.
• Coagulation Panels (PT/INR): May be prolonged in individuals consuming large amounts of Cassia cinnamon.

> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking. The interaction between botanical extracts and pharmaceutical drugs can be unpredictable.

Cinnamon must NEVER be used in the following circumstances:

1. 1Known Hypersensitivity: Individuals with a documented allergy to cinnamon, cinnamaldehyde, or Balsam of Peru should avoid all medicinal forms of cinnamon. The mechanism is a Type I or Type IV hypersensitivity reaction which can lead to anaphylaxis or severe contact dermatitis.
2. 2Severe Hepatic Impairment: Patients with decompensated cirrhosis or acute liver failure must not use cinnamon supplements. The coumarin content in Cassia varieties cannot be adequately metabolized, leading to further hepatocellular damage.
3. 3Active Hemorrhage: Due to the potential anticoagulant effects of coumarin, cinnamon should not be used by patients with active bleeding disorders or major internal bleeding.

Conditions requiring careful risk-benefit analysis include:

• Mild to Moderate Liver Disease: Such as Non-Alcoholic Fatty Liver Disease (NAFLD). The potential for hepatotoxicity may outweigh the metabolic benefits.
• Planned Surgery: As mentioned, the risk of bleeding and glycemic instability makes cinnamon use risky in the perioperative period.
• Pregnancy: High medicinal doses are relatively contraindicated due to the potential for uterine stimulation (emmenagogue effects).
• Peptic Ulcer Disease: Cinnamon can irritate the gastric mucosa, potentially worsening ulcers or gastritis.

Patients should be aware of potential cross-reactions with:

• Balsam of Peru: Frequently used in perfumes and topical medications.
• Cloves and Nutmeg: May share similar aromatic compounds that trigger allergic responses.
• Synthetic Fragrances: Many contain cinnamal, which can trigger reactions in cinnamon-sensitive individuals.

> Important: Your healthcare provider will evaluate your complete medical history before prescribing or recommending Cinnamon extracts.

• Risk Summary: Cinnamon is considered safe when consumed in standard food amounts during pregnancy. However, medicinal doses (supplements) are not recommended.
• Clinical Considerations: Historically, cinnamon has been used as an emmenagogue (a substance that stimulates menstrual flow). In high doses, it may stimulate uterine contractions, potentially increasing the risk of miscarriage or preterm labor. There is insufficient data on the teratogenic potential of concentrated cinnamon extracts in humans.

• Passage into Milk: It is unknown if the bioactive components of cinnamon, such as cinnamaldehyde or coumarin, are excreted in human breast milk.
• Effects on Infant: While culinary use is likely safe, high-dose supplements could potentially affect the nursing infant's liver or blood sugar. Due to the lack of safety data, nursing mothers are advised to avoid cinnamon supplements.

• Safety Profile: The safety of high-dose cinnamon has not been established in children.
• Specific Risks: Children may be more susceptible to the hepatotoxic effects of coumarin due to their smaller body mass and developing liver enzyme systems. Its use as an allergenic extract is limited to diagnostic settings under strict supervision.

• Pharmacokinetic Changes: Older adults often have reduced renal and hepatic clearance. This can lead to the accumulation of coumarin metabolites, increasing the risk of liver injury.
• Polypharmacy: The elderly are more likely to be on multiple medications (anticoagulants, statins, diabetes meds) that interact with cinnamon. Healthcare providers should perform a thorough medication review before recommending cinnamon to older patients.

• Dosing: While no specific GFR-based adjustments exist, the kidneys are the primary route of elimination for cinnamon metabolites. In patients with severe renal impairment, monitoring for systemic toxicity is essential.
• Dialysis: It is unknown if cinnamon's active components are dialyzable.

• Child-Pugh Classification: Cinnamon (especially Cassia) is generally contraindicated in patients with Child-Pugh Class B or C hepatic impairment. The risk of worsening liver function due to coumarin-induced stress is high. Even in Class A (mild) impairment, extreme caution and frequent LFT monitoring are required.

> Important: Special populations require individualized medical assessment to ensure that the use of any botanical extract does not compromise underlying health conditions.

Cinnamon acts through multiple molecular pathways. Its primary metabolic effect is mediated by polyphenol polymers that increase insulin sensitivity. These compounds enhance the activity of the insulin receptor tyrosine kinase and inhibit the enzyme protein tyrosine phosphatase 1B (PTP1B), which normally dephosphorylates (inactivates) the insulin receptor. This results in prolonged insulin signaling. Additionally, cinnamon interacts with Peroxisome Proliferator-Activated Receptors (PPARs), specifically PPAR-gamma and PPAR-alpha, which play key roles in lipid and glucose metabolism. Its action as a Non-Standardized Food Allergenic Extract involves the binding of cinnamon proteins to IgE on mast cells, leading to degranulation.

• Onset of Effect: For blood glucose, effects may be seen within 2-4 weeks of consistent daily use. For allergic reactions, the onset is immediate (minutes) upon contact.
• Duration: The metabolic effects of a single dose typically last 12-24 hours.
• Tolerance: There is no evidence of pharmacological tolerance developing with long-term use, though the risk of side effects may increase over time.

| Parameter | Value |

|---|---|

| Bioavailability | 5-20% (Polyphenols); >70% (Cinnamaldehyde) |

| Protein Binding | 70-80% (Cinnamaldehyde to Albumin) |

| Half-life | 1.5 - 3 hours (Cinnamic acid) |

| Tmax | 1 - 2 hours |

| Metabolism | Hepatic (Oxidation, CYP2A6 for Coumarin) |

| Excretion | Renal (80-90%), Fecal (10-20%) |

• Molecular Components: Cinnamaldehyde (C9H8O), Cinnamic acid (C9H8O2), Coumarin (C9H6O2).
• Molecular Weight: Cinnamaldehyde: 132.16 g/mol; Coumarin: 146.14 g/mol.
• Solubility: Volatile oils are lipid-soluble; polyphenols are water-soluble.
• Structure: Cinnamaldehyde consists of a phenyl group attached to an unsaturated aldehyde.

Cinnamon is classified as a Non-Standardized Food Allergenic Extract [EPC]. Within the therapeutic realm, it is often grouped with other insulin-sensitizing botanicals like Fenugreek and Bitter Melon, though its specific EPC tags include Central Nervous System Stimulant [EPC] and Anti-coagulant [EPC] due to its complex chemical matrix.