Cardiometabolic Benefits

Cardiometabolic benefits of micronutrient supplements vary

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Supplementation of certain micronutrients benefited cardiometabolic health, but others did not, according to a systematic review and meta-analysis.

Specifically, supplementation with omega-3 fatty acids, folic acid and coenzyme Q10 conferred certain benefits, supplementation with vitamin C, vitamin D, vitamin E and selenium had no effect on CVD risk and supplementation with beta-carotene was harmful, researchers wrote in the Journal of the American College of Cardiology.

“For the first time, we developed a comprehensive, evidence-based integrative map to characterize and quantify micronutrient supplements’ potential effects on cardiometabolic outcomes,” Simin Liu, MD, MS, MPH, ScD, professor of epidemiology and medicine at Brown University, said in a press release. “Our study highlights the importance of micronutrient diversity and the balance of health benefits and risks.”

Liu and colleagues analyzed 884 randomized controlled trials evaluating 27 types of micronutrients. The analysis included 883,627 participants and covered 4,895,544 person-years.

Benefits vary

The following micronutrients were associated with moderate- to high-quality evidence for reducing CVD risk factors: omega-3 fatty acids, omega-6 fatty acids, L-arginine, L-citrulline, folic acid, vitamin D, magnesium, zinc, alpha-lipolic acid, coenzyme Q10, melatonin, catechin, curcumin, flavanol, genistein and quercetin, according to the researchers.

Supplementation with omega-3 fatty acids was linked with reduced risk for CVD mortality (RR = 0.93; 95% CI, 0.88-0.97), MI (RR = 0.85; 95% CI, 0.78-0.92) and CHD events (RR = 0.86; 95% CI, 0.8-0.93), while supplementation with folic acid reduced risk for stroke (RR = 0.84; 95% CI, 0.72-0.97) and supplementation with coenzyme Q10 reduced risk for all-cause mortality (RR = 0.68; 95% CI, 0.49-0.94), Liu and colleagues wrote.

There was no relationship between CVD or diabetes risk and supplementation with vitamin C, vitamin D, vitamin E and selenium, and supplementation with beta-carotene increased risk for all-cause mortality (RR = 1.1; 95% CI, 1.05-1.15), CVD mortality (RR = 1.12; 95% CI, 1.06-1.18) and stroke (RR = 1.09; 95% CI, 1.01-1.17), according to the researchers.

“Identifying the optimal mixture of micronutrients is important, as not all are beneficial, and some may even have harmful effects,” Liu said in the release.

More than antioxidant properties

In a related editorial, Juan G. Gormaz, PhD, from the faculty of medicine at the University of Chile in Santiago, and Rodrigo Carrasco, MD, PhD, from the Chilean Society of Cardiology and Cardiovascular Surgery in Santiago, wrote that “Given that the compounds with more pleiotropic properties produced the better outcomes, the antioxidant paradigm on cardiovascular prevention can be challenged. For example, inasmuch as omega-3 fatty acids have antiplatelet and anti-inflammatory properties, they are too complex to enable attribution of the observed benefits solely to their antioxidant capacity.”

The study supports the hypothesis that “only compounds able to have an impact on oxidative stress through more than one pathway and/or that have pleiotropic properties should have a significant clinical effect,” Gormaz and Carrasco wrote.

HDL Subtypes Help Mediate Bariatric Surgery’s Cardiometabolic Benefits

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Cardiometabolic benefits from bariatric surgery in the obese stem more from its favorable lipoprotein-profile “remodeling” effects, in particular to variable changes in HDL subtypes, than on improvements in overall HDL or LDL levels the way they are usually measured in clinical practice, suggested several reports from the European Atherosclerosis Society 2016 Congress.

Although levels of total cholesterol, LDL cholesterol, and triglycerides dropped significantly from baseline to 6 months after Roux-en-Y gastric-bypass surgery, total HDL-cholesterol levels did not change, in a prospective study of 94 patients presented by Dr Gersina Rega-Kaun (Medical University of Vienna, Austria)[1].

The reduction in triglycerides, however, was correlated with a shuffling of HDL-particle subtypes after surgery, such that over 6 months, mean levels of “small, dense” HDL fell from 10 mg/dL to 6 mg/dL (P<0.001) while those of “large, buoyant” HDL rose from 11 mg/dL to 15 mg/dL (P<0.001). The increase in large, buoyant HDL was inversely correlated (P<0.05) with the drop in triglycerides, but not with changes in total or LDL cholesterol, Rega-Kaun reported.
Dr Gersina Rega-Kaun

Larger HDL species appear more atheroprotective than the apolipoprotein-rich smaller ones, in part through antioxidative properties and stimulation of nitric-oxide synthase, according to Rega-Kaun. Her study, she told heartwire from Medscape, suggests that “the surgery remodels the HDL profile, which leads to better antioxidation and anti-inflammatory function, and this contributes to, for example, improved endothelial function.”

In support of those findings, a different group studied 34 obese patients as they followed a prospective plan of diet and lifestyle changes prior to undergoing gastric bypass surgery[2].

Average weight loss reached 10.5% after the preoperative lifestyle changes and 34.7% 1 year after the surgery, reported investigators led by Dr Christian Abendstein Kjellmo (Nordland Hospital, Bodø, Norway).

After the diet and lifestyle changes, total LDL-cholesterol fell significantly (P<0.0001) as did LDL type 1–2 (large, buoyant) and LDL type 3–7 (small, dense) subfractions (P<0.01). All changes persisted a year after surgery, except for the return to baseline for the LDL type 3–7 subfraction.

With diet and lifestyle intervention, total HDL cholesterol fell slightly but significantly (P<0.01) and apolipoprotein-rich small HDL decreased significantly as well (P<0.0001). But a year after bariatric surgery, total HDL-cholesterol had rebounded to significantly higher than baseline (P<0.0001) accompanied by a significant climb in large HDL (P<0.0001).

Interestingly, at no point in the follow-up—not after lifestyle intervention nor a year after surgery—was a change observed in serum cholesterol efflux capacity (Sigma-Aldrich assay).

The findings show contrasting effects of diet/lifestyle changes and bariatric surgery on lipoprotein levels and function and different effects on markers of cardiometabolic health, perhaps, according to the group, secondary to changes in gut microbiota. In short, they “may in part explain the positive effects of bariatric surgery on cardiovascular morbidity and mortality in morbidly obese patients.”

Dr Petia Doytcheva (Center for Molecular Cardiology, Zurich, Switzerland) agreed that the surgery’s effects on relative levels of different HDL subtypes and their different functions seem largely behind its observed survival benefits. “Normally, we measure the total value of HDL in serum, but HDL function is more important,” she said to heartwire .
Dr Petia Doytcheva

It seems to be, she said, that the obese, especially those with diabetes, have a preponderance of small dysfunctional HDL species and therefore impairment of HDL-related reverse cholesterol transport and endothelial function and that those derangements are reversed by bariatric surgery in a way that diet therapy cannot match.

That was the message, she said, from her group’s allocation of 62 patients with a body-mass index exceeding 35 kg/m2 to undergo Roux-en-Y gastric bypass or follow a program featuring a hypocaloric weight-reduction diet and lifestyle-modification counseling, all with medical attention for any diabetes, hypertension, dyslipidemia, or other obesity-related complications[3].

The 32 patients who had surgery lost 25.9 kg over 6 months, compared with 11 kg for the 30 following the diet/lifestyle program (P<0.0001). Total cholesterol, triglycerides, and fasting glucose levels were significantly reduced over the period in both groups, and total HDL cholesterol was significantly increased in both groups. But LDL cholesterol fell significantly only in the group that underwent bariatric surgery.

However, Doytcheva said, levels of small, dense HDL particles were significantly reduced and large, buoyant HDL was significantly raised after 6 months in the bariatric-surgery group but not the diet/lifestyle group, “meaning there was better HDL function after bariatric surgery.”

Furthermore, endothelial nitric-oxide production (measured by DAF-2 fluorescence and paraoxonase-1 antioxidant activity) stimulated by smaller HDL subtypes was improved by 40% after 6 months compared with baseline in the bariatric-surgery group, as compared with only 9% in the diet/lifestyle group (P<0.0001).

That is, weight loss from bariatric surgery, but not conventional weight loss, Doytcheva said, “restored endothelium-protective HDL properties” despite improvements in traditional lipid profiles following both weight-loss strategies.