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If any nutritional intervention has health benefits backed by the scientific literature, it may be the low-salt diet -- but even then, the evidence is only of moderate certainty, a review found.

Reduced salt intake lowered all-cause mortality in normotensive people (RR 0.90, 95% CI 0.85-0.95) and cardiovascular mortality in hypertensive patients (RR 0.67, 95% CI 0.46-0.99), according to researchers led by Safi Khan, MD, of West Virginia University in Morgantown.

"The beneficial effects of reduced salt intake on mortality and CVD [cardiovascular disease] risk reduction remain a debatable issue. Although some data support lower salt intake to reduce CVD risk, other studies have shown a U-shaped relationship between sodium intake and death," Khan's group noted in the Aug. 6 issue of .

Their review included more than 992,000 people across published randomized controlled trials (RCTs) and meta-analyses of these RCTs testing 24 nutritional supplements and dietary interventions.

"The U.S. Department of Health and Human Services and the U.S. Department of Agriculture have been criticized for the paucity of sound scientific background behind their dietary recommendations. Similarly, the U.S. Preventive Services Task Force report has not been updated since 2014," the authors said.

The diet and supplement literature suffers as "most trials are not randomized, are not of sufficient duration, or do not have enough hard outcome events," according to Amitabh Pandey, MD, and Eric Topol, MD, both of Scripps Research and Scripps Clinic in La Jolla, California, in an .

"Only recently with machine learning of large data sets, which include multimodal data on physical activity, sleep, medications, demographic characteristics, intake and timing of all foods and beverages, and gut microbiome constituents, have we begun to learn that the use of any specific diet or supplement is likely to have markedly heterogeneous effects," the editorialists wrote.

Findings of low certainty in Khan's study included omega-3 fatty acids being tied to reduced risk of MI (RR 0.92, 95% CI 0.85-0.99) and coronary heart disease (RR 0.93, 95% CI 0.89-0.98).

Notably, the REDUCE-IT trial had been excluded because it only tested Vascepa's proprietary icosapent ethyl, a highly purified omega-3 pill that does not qualify as a dietary supplement under U.S. law.

On the other hand, stroke risk went up with calcium plus vitamin D supplementation (RR 1.17, 95% CI 1.05-1.30), an observation of moderate certainty according to the investigators. "Potential biological explanations are hypercalcemia-mediated vascular calcifications, triggering of atherosclerosis, and hypercoagulability," they suggested.

"It remains uncertain whether this can be attributed to oversupplementation in a Western diet that already has significant dietary fortification with calcium plus vitamin D," added Pandey and Topol.

Regional differences may also account for folic acid being associated with a lower risk of stroke (RR 0.80, 95% CI 0.67-0.96).

This low-certainty observation was largely driven by a trial from China, where there is no folate fortification of foods, and therefore may not be generalizable to the U.S., Khan and colleagues said.

Other supplements and diets included in their study -- including the Mediterranean diet and a diet of reduced saturated fats -- apparently made no difference in death or cardiovascular disease outcomes.

"There are inherent limitations secondary to the shortcomings of included meta-analyses and RCTs (that is, heterogeneity of baseline characteristics of the participants, including age, sex, health and socioeconomic status, and interventions; lack of dose-response analyses; and variable duration of follow-up)," the study authors acknowledged.

"Unfortunately, the current study leaves us with the same foggy conditions that we started with. Until these conditions clear, it would be reasonable to hold off on any supplement or diet modification in all guidelines and recommendations," Pandey and Topol concluded.

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