High Cholesterol (Hyperlipidemia)

High Cholesterol (Hyperlipidemia)

About 38 percent of US adults carry a total cholesterol at or above 200 mg/dL, and 12 percent have LDL cholesterol at or above 160 mg/dL, thresholds that produce no symptom whatever in the large majority of cases. Xanthomas, corneal arcus and xanthelasma appear only in severe or familial forms. Ten ingredients are graded against lipid endpoints here, on 251 studies and roughly 37,000 participants, and four reach Grade A, the highest proportion of strong-evidence entries of any cardiovascular condition in this collection.

Three of those four work by a physical principle rather than a pharmacological one. Plant sterols and stanols, the widest-studied ingredient in the set at 84 studies and 5,000 participants, compete with dietary and biliary cholesterol for space in intestinal micelles, so less is absorbed. Psyllium, on 28 studies and 2,000 participants, and beta-glucan, on 28 studies and 2,500 participants, form viscous gels that bind bile acids and increase their loss in stool, obliging the liver to draw on circulating cholesterol to synthesise replacements. The gel-forming behaviour of psyllium has been characterised in detail in pharmaceutical work on the same material ^[1].

Red yeast rice is the exception among the Grade A entries, and the reason for its rating on 22 studies and 8,000 participants is that it does not behave like a food. It contains monacolin K, structurally identical to the statin lovastatin, and inhibits the same rate-limiting enzyme of cholesterol synthesis. A multicentre randomised trial in adults with mild dyslipidaemia paired low-dose monacolin K with coenzyme Q10, grape seed and olive leaf extracts and reported lower LDL cholesterol in the supplemented group ^[2]. Its regulatory status differs between jurisdictions for that reason, and its adverse-effect profile resembles low-dose statin therapy rather than dietary fibre.

Two ingredients hold Grade B. Berberine rests on 46 studies and 5,000 participants and is thought to act largely by upregulating hepatic LDL-receptor expression, a route distinct from that of the statins. Niacin sits on only 10 studies but 12,000 participants, a shape that reflects its history: it was tested in large cardiovascular outcome trials rather than in many small lipid studies, and the outcome results tempered the enthusiasm the lipid results had generated.

The four Grade C entries are held back by narrow evidence rather than by contradictory findings. Chitosan has 14 studies and 1,100 participants, curcumin 7 and 500, krill oil 7 and 600, astaxanthin 5 and 300. A randomised trial of curcumin with coenzyme Q10 in people with metabolic syndrome examined the metabolic-control endpoints that overlap with lipid management ^[3], while much of the krill oil work remains preclinical, including a rodent study of hypercholesterolaemia and hepatic fat ^[4]. The human literature on astaxanthin is broader in scope than in depth, spanning several tissues at modest trial sizes ^[5].

All ten entries are recorded with a positive direction, which is a statement about consistency rather than about magnitude. Saturated and trans fat intake, body weight, physical inactivity and untreated hypothyroidism remain the determinants with the largest effect on the same laboratory values.