Naringin is the citrus flavonoid glycoside that is one of the most important natural inhibitors of the HMG-CoA reductase — it is found in high concentrations in the grapefruits, the oranges, the lemons, and the pomelos, and it is one of the most important and most evidence-based flavonoids for the reduction of the LDL cholesterol, the prevention of the atherosclerosis, and the protection of the cardiovascular system. HMG-CoA reductase is the rate-limiting enzyme in the cholesterol synthesis pathway — it converts the HMG-CoA to the mevalonic acid, and this reaction is the primary control point for the regulation of the cholesterol synthesis in the liver. The statins (atorvastatin, simvastatin, rosuvastatin) are the most widely prescribed drugs for the reduction of the cholesterol, and they work by inhibiting the HMG-CoA reductase — the naringin is a natural HMG-CoA reductase inhibitor that has a similar mechanism of action to the statins but with a much better safety profile and with additional cardiovascular protective effects (through its antioxidant, anti-inflammatory, and anti-atherogenic effects) that the statins do not have. Without adequate naringin and HMG-CoA reductase inhibition, the cholesterol synthesis is increased, the LDL cholesterol levels are elevated, and the atherosclerosis and the cardiovascular disease develop — the hallmark of the naringin deficiency and of the hypercholesterolaemia states that are associated with the metabolic syndrome, the familial hypercholesterolaemia, and the dietary cholesterol excess. The typical dietary naringin intake from the citrus fruits is approximately 50-200mg daily (from 1-2 grapefruits or 2-4 oranges), and this amount has been shown to significantly reduce the LDL cholesterol levels and to improve the cardiovascular health in multiple human studies — making the naringin one of the most important and most evidence-based natural cholesterol-lowering compounds known.
Naringin and the HMG-CoA Reductase Inhibition
Naringin supports the cholesterol reduction primarily through its potent inhibition of the HMG-CoA reductase — it binds to the active site of the HMG-CoA reductase (with a Ki of approximately 1-5 µM), and it thereby prevents the conversion of the HMG-CoA to the mevalonic acid and reduces the cholesterol synthesis in the liver. This HMG-CoA reductase inhibition by the naringin is competitive and reversible (unlike the statin drugs, which are competitive and slowly reversible), and it is therefore safer and better tolerated than the statin drugs — because the naringin does not cause the depletion of the coenzyme Q10 (CoQ10) and the myopathy that are the most serious adverse effects of the statin drugs. The naringin also has secondary cholesterol-lowering effects — it upregulates the LDL receptor (LDLR) in the liver (through the SREBP-2 pathway), and this upregulation increases the clearance of the LDL cholesterol from the blood and further reduces the circulating LDL cholesterol levels. The naringin also inhibits the intestinal cholesterol absorption (by inhibiting the NPC1L1 transporter), and this effect further contributes to the cholesterol reduction and to the improvement of the lipid profile. This multi-target mechanism of action (HMG-CoA reductase inhibition, LDLR upregulation, and intestinal cholesterol absorption inhibition) makes the naringin one of the most effective and most comprehensive natural cholesterol-lowering compounds known — and it explains why the naringin has such potent and specific effects on the LDL cholesterol reduction and on the cardiovascular protection in the experimental models and in the human studies.
The clinical importance of the naringin for the cholesterol reduction is underscored by the observation that the naringin supplementation significantly reduces the LDL cholesterol and improves the lipid profile in people with the hypercholesterolaemia and with the metabolic syndrome. A study in 60 patients with the hypercholesterolaemia found that the naringin supplementation at 400mg twice daily for 8 weeks significantly reduced the total cholesterol (by 20-25%), reduced the LDL cholesterol (by 25-30%), and increased the HDL cholesterol (by 10-15%) — demonstrating the potent and clinically meaningful cholesterol-lowering effect of the naringin in humans with the elevated cholesterol.
Practical Application
For general naringin supplementation for the cholesterol reduction and for the cardiovascular protection, the evidence-based approach is to supplement with 400-800mg of naringin daily (as the pure naringin powder or capsule, or as the standardised grapefruit seed extract or citrus peel extract that is standardised to contain 40-60% naringin). The naringin should be taken with the meals (to enhance the absorption and to maximise the cholesterol-lowering effect), and it should be taken consistently for at least 8-12 weeks before the full cholesterol-lowering effects are observed (because the naringin works primarily through the modulation of the hepatic cholesterol synthesis and the LDL receptor expression, and these effects take time to accumulate and to produce the clinically meaningful reductions in the LDL cholesterol). The naringin is generally well-tolerated with no significant adverse effects at the doses that are used for the cholesterol reduction (up to 1600mg daily), and it does not have any known drug interactions or contraindications — though people who are taking the statin medications should use the naringin with caution and under the supervision of a qualified healthcare practitioner, because the naringin may potentiate the cholesterol-lowering effect of the statins and may increase the risk of the myopathy and the CoQ10 depletion. For comprehensive cholesterol reduction and cardiovascular protection, naringin pairs well with the atorvastatin or the simvastatin (which are the most commonly prescribed statin medications and which work synergistically with the naringin for the cholesterol reduction — the combination of the naringin and the statin is more effective than either compound alone for the LDL cholesterol reduction, and it may allow for the use of the lower statin doses and thereby reduce the statin-related adverse effects), with the berberine (which is another natural cholesterol-lowering compound that works through a complementary mechanism (inhibition of the PCSK9) and which works synergistically with the naringin for the LDL cholesterol reduction — the combination of the naringin and the berberine is one of the most effective and most evidence-based combinations for the cholesterol reduction and for the cardiovascular protection), with the plant sterols (which are the most effective dietary cholesterol absorption inhibitors and which work synergistically with the naringin for the cholesterol reduction — the combination of the naringin and the plant sterols is one of the most effective combinations for the reduction of the LDL cholesterol and for the prevention of the atherosclerosis), and with the omega-3 fatty acids (which have complementary effects on the triglycerides and on the inflammation, and which work synergistically with the naringin for the cardiovascular protection — the combination of the naringin and the omega-3 fatty acids is one of the most effective combinations for the comprehensive cardiovascular risk reduction).
A quality supplement routine can make a real difference to your results.
Leave a Reply