The Many Faces Of Schisandra, from Detoxification, Lipid Metabolism, and Acetyl-Aldehyde

*This article is not medical advice. Before starting on any health related regimen, seek the advice of your Primary Care Physician or an M.D.

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Schisandra

Without a doubt, Schisandra is one my favorite herbs, but it doesn’t mean its right for all situations, but rather specific ones i see often.

Schisandra upregulates ALDH2, the last gene in the pathway to clear Acetyl Aldehyde out of the body. Many of our East Asian friends have significant compromise on this gene, which results in flushing with alcohol consumption.

All About Schisandra In Short:

It supports various functions, summarized below:

1. Lipid Metabolism

2. Hepatic Anti Oxidant Defense

3. Detoxification

4. Bile Acid & Cholesterol Detox Genes

5. Induces Key CYP3A4 genes - to help with drug metabolism

6. Transcription Factor Modulation

7. Acetyl Aldehyde Clearance

Lipid Metabolism

Some of the more impactful effects from Schisandra regarding lipid metabolism are summarized below:

1. Stimulates PPAR Alpha - master regulator of fatty acid oxidation in the liver

2. Stimulates CPT1A - increased transport of carnitine

3. Stimulates ACOX1 - increased mitochondrial peroxisimal and Beta-oxidation

4. Reduces FASN - Fatty Acid Synthase; reduced de novo lipogensis

5. Reduces SREBF1 - Lipogensis Transcription Factor

6. Reduces DGAT2 - Triglyceride synthesis; helps NAFLD

7. Reduces HMGCR - Lowering cholesterol synthesis

8. Increases LDLR - increases expression of LDL receptor, increasing LDL clearance

Bile Acid & Cholesterol Detox Genes

A summary of the mechanisms that Schisandra effects to improve bile flow, bile acid clearance, and cholesterol excretion:

1. Induces FXR (Farsenoid X Receptor / NR1H4) - regukates bile acid synthesis, increases BSEP / ABC11 (Bile Salt Export Pump - valve from liver to gallbladder), and lower CYP7A1 (Super Important to Account For)

2. Lowers CYP7A1 via FXR induction and feedback

3. Induces ABCB11 / BSEP - as above, increases bile acid efflux

4. Increases MRP2 / ABCC2 (Chaperone of toxins into bile after they leave phase 2 conjugation - super important) - increases expression leading to organic anion efflux

5. Increases SLCO1B1 / SLC O1B3 - hepatic uptake of bile acids and billilrubin, also processes Copoporhyrin I and III.

Liver Anti Oxidant and Cyto Protective Genes - Via NrF2

1. Increases GCLC / GCLM

2. Increases SOD1, SOD2

3. Increases CAT

4. Increases GPX1/4

5. Increases PRDX’s - especially PRDX3 in mitochondria

6. Increases TRNDX’s

7. Increases HMOX1/2

Detoxification and Xenobiotic Metabolism Genes

1. Increases CYP3A4 - strong induction via PXR

2. Increases CYP2B6 - strong induction via CAR

3. Increases CYP2C9/19 - Induced

4. Increases UGT1A1 - Increased activity and expression

5. Increases UGT1A9/2B7 - Increased activity and expression

6. Increases SULT1A1/2A1 - Increased activity

7. Increases GSTP1/A1/M1 - Increased activity and expression

8. Increases NQO1 - Increased via Nrf2

Transcription Factor Modulation

1. NrF2 - Anti Oxidant Defense and Phase 2 Detox

2. PPAR Alpha - Fatty Acid Beta Oxidation

3. PXR (NR1i2) - CYP3A4, UGT Induction

4. CAR (NR1i3) - CYP2B6, UGT Induction

5. FXR (NR1H4) - bile acid regulation

6. SREBPC1 - lipogenisis expression

Acetyl Aldehyde Clearance

The last gene in the clearance of acetyl aldehyde is ALDH2, cofactors being NAD, Magnesium, Zinc, and Cysteine resides. Inputs into this pathway from gut dysbiosis, fungal overgrowth, candida, alcohol intake, carbohydrates and sugar intake all contribute to acetyl aldehyde formation in addition to histamine! There are important genetic mutations that can significantly downregulate ALDH2, leading to more overload as well. Schizandra mildly stimulates ALDH2 which can help lower acetyl aldehyde levels.

Counter Indications To Give Some Pause

1. Low NAD

2. Low Magnesium or Zinc

3. Homozygous mutations on CYP7A1

This is a draft of this blog article, references and additions forthcoming!

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References: