Beyond Nutrient Deficiency-Opportunities to Improve Nutritional Status and Promote Health Modernizing DRIs and Supplementation Recommendations

Abstract

The US Dietary Guidelines for Americans (DGA) provide dietary recommendations to meet nutrient needs, promote health, and prevent disease. Despite 40 years of DGA, the prevalence of under-consumed nutrients continues in the US and globally, although dietary supplement use can help to fill shortfalls. Nutrient recommendations are based on Dietary Reference Intakes (DRIs) to meet the nutrient requirements for nearly all (97 to 98 percent) healthy individuals in a particular life stage and gender group and many need to be updated using current evidence. There is an opportunity to modernize vitamin and mineral intake recommendations based on biomarker or surrogate endpoint levels needed to 'prevent deficiency' with DRIs based on ranges of biomarker or surrogate endpoints levels that support normal cell/organ/tissue function in healthy individuals, and to establish DRIs for bioactive compounds. We recommend vitamin K and Mg DRIs be updated and DRIs be established for lutein and eicosapentaenoic and docosahexaenoic acid (EPA + DHA). With increasing interest in personalized (or precision) nutrition, we propose greater research investment in validating biomarkers and metabolic health measures and the development and use of inexpensive diagnostic devices. Data generated from such approaches will help elucidate optimal nutrient status, provide objective evaluations of an individual's nutritional status, and serve to provide personalized nutrition guidance.

Keywords: DRIs; EPA and DHA; dietary guidelines; lutein; magnesium; nutritional status; vitamin K.

Figure 1

Serum 25(OH)D concentration relationship with different structural or functional outcomes. (A). Serum 25(OH)D concentrations relationship with sit-to-stand time in adults with mean age 71 years (49% female) controlled for sex, age (5-year categories), race/ethnicity, BMI, poverty income ratio, daily calcium intake, number of medical comorbidities, use of a walking device, self-reported arthritis, activity level, and month of vitamin D measurement. From [47]. (B). Serum 25(OH)D concentration relationship with bone mineral density in adults ≥50 years after adjustment for sex, age, BMI, smoking, calcium intake, estrogen use, month of vitamin D measurement, and poverty income ratio. From [47]. (C). Spline curve describing the association between 25(OH)D concentration and recurrent fallers in the total population. From [49]. (D). The association between serum 25(OH)D level and total bone mineral density from NHANES 2001–2006 among 5990 adolescents (12–19 years). Solid red line represents the smooth curve fit between variables. Blue band represents the 95% confidence interval from the fit. Adjusted for age, gender, race/ethnicity, income to poverty ratio, education, physical activity, body mass index, calcium use. From [50]. Vertical line indicates vitamin D deficiency cutoff, i.e., serum 25(OH)D < 30 nmol/L (red), used in setting DRI [46] and insufficiency cutoff, i.e., serum 25(OH)D < 50 nmol/L (green), used in updating DRI [26].

Figure 2

Dose–response association between vitamin C concentration and risk of total CVD mortality with 95% CI from 6 studies with 45,040 participants and 2992 cases. From [56]. Vertical red line indicates vitamin C deficiency, i.e., blood ascorbic acid < 11.4 µmol/L, used in setting DRI [28].

Figure 3

Serum lutein and macular pigment optical density (MPOD). Rate of change of MPOD (milli-Absorbance units) as a function of fractional change in serum lutein concentration (plateau value minus pre-supplementation value, divided by pre-supplementation value). Data from 46 healthy subjects randomly assigned to 0, 5, 10, and 20 mg of free, unesterified lutein in soft-shell gelatin capsules and whose standard deviations in the rates of change of MPOD were <0.250. From [83].

Figure 4

Multivariate-adjusted relationship of blood long-chain, omega-3 fatty acids with all-cause mortality. De novo pooled analysis using data from 17 prospective cohort studies with a median 16 y follow-up, 15,720 deaths among 42,466 participants, and an average baseline age of 65 years. The solid lines and shaded area represent the best estimates and 95% CI, respectively. The 10th percentile was selected as a reference level (HR = 1) and the x-axis depicts 5th to 95th percentiles. Potential nonlinearity was identified for EPA (p = 0.0004) but not for others (p > 0.05). All HRs are adjusted for age, sex, race, field center, body-mass index, education, occupation, marital status, smoking, physical activity, alcohol intake, prevalent diabetes, hypertension, and dyslipidemia, self-reported general health, and the sum of circulating 6 polyunsaturated fatty acids (linoleic plus arachidonic acids). From [129].

Figure 5

Forest plots showing the effect of vitamin K supplementation。 (A) % change in vascular calcification. (B) Vascular stiffness. (C) Serum dephospho-uncarboxylated matrix Gla protein (dp-ucMGP). (D) serum uncarboxylated osteocalcin (ucOC). Data are presented as mean % difference and 95% CI. From [168].

Figure 6

Adjusted hazard ratios of serum magnesium with all-cause mortality in the US adult population (NHANES I 1971–2011). The solid curve is HR calculated by restricted cubic splines with knots at serum Mg levels of 0.73, 0.82, 0.87, and 0.96 mmol/L, a reference HR = 1 set at 0.80 mmol/L, and adjusted using weighted Cox regression model for age, sex, race/ethnicity, education, family income, smoking, alcohol, physical activity, BMI, history of diabetes, hypertension, and vitamin and/or mineral supplement uses. From [190]. Vertical red line indicates magnesium depletion cutoff, i.e., serum Mg concentration <0.75 mmol/L, used in setting DRI [46].