The Role of Nutrition and Nutritional Supplements in the Treatment of Dyslipidemia

Mark Houston

Clin Lipidology. 2014;9(3):333-354.

Vitamin C

Vitamin C supplementation lowers serum low-density lipoprotein cholesterol and triglycerides.^[172] A meta-analysis of 13 randomized controlled trials in subjects given at least 500 mg of vitamin C daily for 3 to 24 weeks found a reduction in LDL cholesterol of 7.9 mg/dl (p < 0.0001) TG reduction of 20.1 mg/dl (p < 0.003). HDL did not change. The reductions in LDL and TG were greatest in those with the highest initial lipid levels and the lowest serum vitamin C levels.^[173]

Lycopene

Lycopene is an acyclic carotenoid with a high concentration in tomatoes. It has been shown in tissue culture to inhibit HMG CoA reductase, induce Rho inactivation, increase PPAR-γ, LXR receptor and RXR activities, increase reverse cholesterol transport and efflux with ABCA1, apo AI expression and caveolin -1 expression, increase HDL 2 and 3, improve HDL functionality, reduce SAA, decrease CETP, increase PON 1 and reduce inflammation in humans..^[174–176] This reduces intracellular cholesterol and lowers cholesterol in lipid domains, which alters membrane-induced cellular signal transduction. The two unconjugated double bonds in the lycopene molecule have high activity against ROS. Higher serum lycopene levels are associated with reduction in carotid IMT and carotid atherosclerosis.^[177]

Wogonin & Flavonoids

Wogonin is a flavonoid (Scutellaria baicalensis Georgi extract) that enhances reverse cholesterol transport..^[178] Wogonin increases the protein expression, level and half-life of the ABCA-1 transporter (ATP binding cassette transporter A-1). This effect is linked to its ability to stimulate PP2B, which is a protein Ser/Thr phosphatase that regulates the stability of ABCA1 protein. In addition, Wogonin inhibits the expression of proatherogenic molecules in endothelial cells and vascular smooth muscle cells. Other flavonoids such as procyanidins, quercetin, catechins, red wine, resveratrol, grape seed extract, tangerine extract and anthocyanins may have similar effects.

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Table 1. Summary of nutraceutical supplement recommend doses for the treatment of dyslipidemia.
Supplement	Daily dose
Niacin: vitamin B3	500–4000 mg in divided doses
Phytosterols	2.15 g
Soy (fermented)	30–50 g
EGCG	500–1000 mg
Omega 3 fatty acids	3000–5000 mg
Flax seed	40 g
Monounsaturated fats	20–40 g
Sesame	40 g
γ/δ tocotrienols	200 mg
Pantethine	900 mg in divided doses
Resveratrol (trans form)	250 mg
N-acetyl cysteine	2000 mg in divided doses
Curcumin	2000–5000 mg in divided doses
Pomegranate juice	8 ounces
Pomegranate seeds	1 cup
Citrus bergamot	1000 mg
Vitamin C	500 mg
Quercetin	500–1000 mg

EGCG: Epigallocatechin gallate.

Box 1. 38 mechanisms for treatment of dyslipidemia-induced vascular disease.
Decrease endothelial permeability, gap junctions, endothelial dysfunction and improve endothelial repair: aged garlic. Increase NO, reduce A-II effects, increase EPC's, BP control, reduce inflammation, oxidative stress and vascular immune dysfunction Modify caveolae, caveolin-1, lipid rafts, membrane microdomains, unesterified cholesterol and cholesterol crystals. Lycopene, omega 3 fatty acids and statins Increase eNOS and nitric oxide. Arginine/citrullene, resveratrol, flax seed, omega 3 fatty acids, co-enzyme Q 10, R-lipoic acid, NAC, taurine, pycnogenol, grape seed extract, pomegranate, aged garlic Modify PRR activation and toll like receptors. Niacin, EGCG, pantethine, resveratrol, MUFA, curcumin, pomegranate, aged garlic, sesame, γ/δ tocotrienols, lycopene Decrease cholesterol crystals, LDL phospholipids, ox-LDL, APO-B and seven ketosteroids that activate PRR. Omega 3 fatty acids and statins Decrease LDL burden (Box 4) Reduce cholesterol absorption (Box 6) Increase cholesterol bile excretion (Box 17) Decrease LDL particle number (Box 13) Decrease APO B (Box 15) Decrease LDL modification/oxidation: (Box 2) Inhibit LDL glycation (Box 3) Increase LDL size (Box 5) Modify LDL composition. Omega 3 fatty acids, MUFA, reduce inflammation, oxidative stress and immune dysfunction Upregulate LDL receptor (Box 17) Regulate sortilins and SORLA Deactivate the LOX-1 receptor. Reduce BP, reduce hsCRP Decrease modified LDL macrophage uptake by scavenger receptors (Box 11) Decrease native LDL macrophage uptake by pinocytosis. Decrease infections and inflammation, decrease modified LDL Decrease LDL signaling. Plant sterols Decrease CAMs, macrophage recruitment and migration. NAC, resveratrol, luteolin, glutathione, and curcumin. Alter macrophage phenotype. Omega 3 fatty acid, plant sterols, sterolins and glycosides Modify signaling pathways Plant sterols and phytosterolins Increase reverse cholesterol transport (Box 12) Increase HDL and increase HDL size (Box 10) Improve HDL function. Reduce inflammation, oxidative stress and immune dysfunction, quercetin, pomegranate, EGCG, resveratrol, glutathione, lycopene Increase APO-A1 (Box 16) Increase PON 1 and PON (Box 18) Reduce inflammation (Box 14) Reduce oxidative stress Modulate immune dysfunction. Plant sterols and sterolins Decrease VLDL and TG (Box 9) Lower Lp(a) (Box 8) Reduce foam cell and fatty streak formation. Resveratrol, NAC, phytosterolins Reduce trapping of foam cells in the subendothelium. Resveratrol, NAC Stabilize plaque. Omega 3 fatty acids, vitamin K2MK7, aged garlic Reduce LpPLA2. Omega 3 fatty acids, niacin Reduce plaque burden, progression and increase regression. Omega 3 fatty acids, vitamin K2 MK 7, aged garlic, pomegranate
BP: Blood pressure; CAM: Cell adhesion molecule; EGCG: Epigallocatechin gallate; eNOS: Endothelial nitric oxide synthase; EPC: Endothelial progenitor cell; MUFA: Monounsaturated fats; NAC: N- acetyl cysteine; NO: Nitric oxide; PRR: Pattern recognition receptor.

Box 2. Inhibition of LDL.
Oxidation Niacin EGCG and catechins Quercetin Pantethine Resveratrol Red Wine Grape Seed extract MUFA Curcumin Pomegranate Garlic Sesame γ/δ tocotrienols Lycopene Polyphenols Flavonoids Oleic acid Glutathione Citrus bergamot Tangerine extract Policosanol RBO (ferulic acid gammaoryzanol) Coenzyme Q 10 Vitamin E Polyphenols and flavonoids
ECGC: Epigallocatechin gallate; MUFA: Monounsaturated fats.

Box 3. Inhibition of LDL glycation.
Carnosine Histidine Myricetin Kaempferol Rutin Morin Pomegranate Organosulfur compounds

Box 4. Lower LDL.
Niacin RYR Plant sterols Sesame Tocotrienols (γ/δ) Pantethine GLA Citrus bergamot EGCG Omega 3 fatty acids Flax Seed MUFA Aged garlic Resveratrol Curcumin Orange juice Soluble fiber Soy Lycopene Fiber
ECGC: Epigallocatechin gallate; MUFA: Monounsaturated fats; RYR: Red yeast rice.

Box 5. Convert dense LDL-B to large LDL-A.
Niacin Omega 3 fatty acids Plant sterols

Box 6. Reduce intestinal cholesterol absorption.
Plant sterols Soy EGCG Flax Seeds Sesame Garlic Fiber
EGCG: Epigallocatechin gallate.

Box 7. HMG CoA reductase inhibition.
RYR Pantethine γ/δ/tocotrienols Sesame EGCG Omega 3 fatty acids Citrus bergamot Garlic Curcumin GLA Plant sterols Lycopene Soy
EGCG: Epigallocatechin gallate; RYR: Red yeast rice.

Box 8. Lower Lp(a).
Niacin N -acetyl cysteine γ/δ tocotrienols Omega 3 fatty acids Flax seed Coenzyme Q 10 Vitamin C L Carnitine L-Lysine L-Arginine Almonds

Box 9. Lower triglycerides.
Niacin RYR Omega 3 fatty acids Pantethine Citrus bergamot Flax seed MUFA Resveratrol Orange juice
MUFA: Monounsaturated fats; RYR: Red yeast rice.

Box 10. Increase total HDL and HDL 2 b levels and convert HDL 3 to HDL 2 and 2 b.
Niacin Omega 3 fatty acids Pantethine Red yeast rice MUFA Resveratrol Curcumin Pomegranate Orange juice Citrus bergamot
MUFA: Monounsaturated fats.

Box 11. Alter scavenger receptor NADPH oxidase and oxidized LDL uptake into macrophages.
Resveratrol N -acetyl cysteine Aged garlic

Box 12. Alter scavenger receptor NADPH oxidase and oxidized LDL uptake into macrophages.
Niacin Plant sterols Glutathione Wogonin Resveratrol Various flavonoids and anthocyanins Alpha linolenic acid

Box 13. Decrease LDL particle number.
Niacin Omega 3 fatty acids

Box 14. Reduce inflammation.
Niacin Omega 3 fatty acids Flax seed MUFA Plant sterols Guggulipids Resveratrol Glutathione Quercetin Curcumin Aged garlic
MUFA: Monounsaturated fats.

Box 15. Lower APO B lipoprotein.
Niacin Omega 3 fatty acids Plant sterols EGCG
EGCG: Epigallocatechin gallate.

Box 16. Increase APO A-1 lipoprotein.
Niacin

Box 17. Upregulate the LDL receptor.
EGCG Sesame Tocotrienols Curcumin Policosanol Plant sterols
EGCG: Epigallocatechin gallate.

Box 18. Increase PON 1 and PON 2.
EGCG Ouercetin Pomegranate Resveratrol Glutathione
EGCG: Epigallocatechin gallate.

Box 19. Increase bile acid excretion.
Resveratrol Citrus bergamot Fiber Probiotics Plant sterols Sesame

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The Role of Nutrition and Nutritional Supplements in the Treatment of Dyslipidemia

Vitamin C

Lycopene

Wogonin & Flavonoids

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References

Authors and Disclosures

Authors and Disclosures

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