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Postdoctoral Researcher, Purdue University


I examine cardiovascular and bone health in response to drinking milk or dairy-free alternatives

The proportion of elderly in the U.S. is fast increasing as is the cost of age-associated diseases, such as cardiovascular disease and osteoporosis. Plant-derived milk alternatives are gaining popularity as a food-based approach to prevent these conditions, yet their effect on cardiovascular and bone health is largely unknown. Dairy foods have been previously shown to mitigate the risk of heart disease and osteoporosis. The purpose of my research project is to compare cow’s milk (fat-free and whole) to a wide range of commercially available plant-based beverages (soy, rice, almond, and coconut drinks) in terms of their effect on calcium absorption and vascular function in adults with metabolic syndrome. In order to quantify calcium absorption, I will use stable isotopes of calcium as calcium labels and measure their appearance in plasma after beverage consumption. To asses vascular function, I will measure the response of small blood vessels in the skin a mild heat stimulus applied 2.5 hours after the absorption of milk proteins. My research hypothesis is that I will observe a relatively higher calcium absorption and a greater skin vascular response in participants consuming dairy milk compared with plant-based beverages. The knowledge gained from this project will help educate the consumers about the value of milk substitutes in prevention of chronic diseases.


Lack of Evidence Linking Calcium With or Without Vitamin D Supplementation to Cardiovascular Disease in Generally Healthy Adults: A Clinical Guideline From the National Osteoporosis Foundation and the American Society for Preventive Cardiology.

Abstract: Calcium is the dominant mineral present in bone and a shortfall nutrient in the American diet. Supplements have been recommended for persons who do not consume adequate calcium from their diet as a standard strategy for the prevention of osteoporosis and related fractures. Whether calcium with or without vitamin D supplementation is beneficial or detrimental to vascular health is not known.The National Osteoporosis Foundation and American Society for Preventive Cardiology convened an expert panel to evaluate the effects of dietary and supplemental calcium on cardiovascular disease based on the existing peer-reviewed scientific literature. The panel considered the findings of the accompanying updated evidence report provided by an independent evidence review team at Tufts University.The National Osteoporosis Foundation and American Society for Preventive Cardiology adopt the position that there is moderate-quality evidence (B level) that calcium with or without vitamin D intake from food or supplements has no relationship (beneficial or harmful) to the risk for cardiovascular and cerebrovascular disease, mortality, or all-cause mortality in generally healthy adults at this time. In light of the evidence available to date, calcium intake from food and supplements that does not exceed the tolerable upper level of intake (defined by the National Academy of Medicine as 2000 to 2500 mg/d) should be considered safe from a cardiovascular standpoint.

Pub.: 25 Oct '16, Pinned: 31 Dec '17

Calcium Intake and Cardiovascular Disease Risk: An Updated Systematic Review and Meta-analysis.

Abstract: Conflicting evidence exists regarding potential cardiovascular risks associated with high levels of calcium intake.To update and reanalyze 2 systematic reviews to examine the effects of calcium intake on cardiovascular disease (CVD) among generally healthy adults.MEDLINE; Cochrane Central Register of Controlled Trials; Scopus, including EMBASE; and previous evidence reports from English-language publications from 1966 to July 2016.Randomized trials and prospective cohort and nested case-control studies with data on dietary or supplemental intake of calcium, with or without vitamin D, and cardiovascular outcomes.Study characteristics and results extracted by 1 reviewer were confirmed by a second reviewer. Two raters independently assessed risk of bias.Overall risk of bias was low for the 4 randomized trials (in 10 publications) and moderate for the 27 observational studies included. The trials did not find statistically significant differences in risk for CVD events or mortality between groups receiving supplements of calcium or calcium plus vitamin D and those receiving placebo. Cohort studies showed no consistent dose-response relationships between total, dietary, or supplemental calcium intake levels and cardiovascular mortality and highly inconsistent dose-response relationships between calcium intake and risks for total stroke or stroke mortality.CVD disease outcomes were secondary end points in all trials. Dose-response metaregression analysis of cohort studies was limited by potential confounding, ecological bias, and imprecise measures of calcium exposures. Data were scarce regarding very high calcium intake-that is, beyond recommended tolerable upper intake levels.Calcium intake within tolerable upper intake levels (2000 to 2500 mg/d) is not associated with CVD risk in generally healthy adults.National Osteoporosis Foundation.

Pub.: 25 Oct '16, Pinned: 31 Dec '17

Effects of Calcium, Vitamin D, and Hormone Therapy on Cardiovascular Disease Risk Factors in the Women's Health Initiative: A Randomized Controlled Trial.

Abstract: To analyze the treatment effect of calcium+vitamin D supplementation, hormone therapy, both, and neither on cardiovascular disease risk factors.We conducted a prospective, randomized, double-blind, placebo-controlled trial among Women's Health Initiative (WHI) participants. The predefined primary outcome was low-density lipoprotein cholesterol (LDL-C).Between September 1993 and October 1998, a total of 68,132 women aged 50-79 years were recruited and randomized to the WHI-Dietary Modification (n=48,835) and WHI-Hormone Therapy trials (n=27,347). Subsequently, 36,282 women from WHI-Hormone Therapy (16,089) and WHI-Dietary Modification (n=25,210) trials were randomized in the WHI-Calcium+Vitamin D trial to 1,000 mg elemental calcium carbonate plus 400 international units vitamin D3 daily or placebo. Our study group included 1,521 women who participated in both the hormone therapy and calcium+vitamin D trials and were in the 6% subsample of trial participants with blood sample collections at baseline and years 1, 3, and 6. The average treatment effect with 95% confidence interval, for LDL-C, compared with placebo, was -1.6, (95% confidence interval [CI] -5.5 to 2.2) mg/dL for calcium+vitamin D alone, -9.0 (95% CI -13.0 to -5.1) mg/dL for hormone therapy alone, and -13.8 (95% CI -17.8 to -9.8) mg/dL for the combination. There was no evidence of a synergistic effect of calcium+vitamin D+hormone therapy on LDL-C (P value for interaction=.26) except in those with low total intakes of vitamin D, for whom there was a significant synergistic effect on LDL (P value for interaction=.03).Reductions in LDL-C were greater among women randomized to both calcium+vitamin D and hormone therapy than for those randomized to either intervention alone or to placebo. The treatment effect observed in the calcium+vitamin D+hormone therapy combination group may be additive rather than synergistic. For clinicians and patients deciding to begin calcium+vitamin D supplementation, current use of hormone therapy should not influence that decision.ClinicalTrials.gov, https://clinicaltrials.gov, NCT00000611.

Pub.: 08 Dec '16, Pinned: 31 Dec '17

Biomarkers of dairy fat intake and risk of cardiovascular disease: a systematic review and meta analysis of prospective studies.

Abstract: Circulating biomarkers of dairy fat provide objective measures of dairy fat intake and facilitate conclusions relevant to populations with different diets and susceptibility to cardiovascular diseases (CVD).To assess the relationship between circulating pentadecanoic acid (15:0), heptadecanoic acid (17:0) and trans-palmitoleic acid (trans-16:1n-7) and the risk of CVD.Pubmed, Medline and Embase were searched for prospective cohort studies of the relationship between biomarkers of dairy fat and CVD risk, which included coronary heart disease (CHD), stroke, heart failure and CVD mortality, supplemented by bibliographies of retrieved articles and previous reviews. For each study, relative risks (RR) and 95% confidence intervals (CI) were extracted and pooled with the random effect model.Thirteen studies involving 7,680 CVD cases were included. The pooled RRs of the risk of CVD for the top third vs. bottom third 15:0, 17:0 and trans-16:1n-7 level were 0.94 (95% CI: 0.77-1.15), 0.82 (95% CI: 0.68-0.99) and 0.82 (95% CI: 0.67-1.02), respectively. Subgroup analysis indicated that there were no associations between the concentration of 15:0 with CHD and stroke, but a negative relationship with heart failure (RR = 0.72, 95% CI: 0.55-0.95). Null association was observed between circulating 17:0 and trans-16:1n-7 level and subtypes of CVD except for only one study which reported a negative relationship between 17:0 and heart failure.Higher diary fat exposure is not associated with an increased risk of CVD.

Pub.: 22 Dec '16, Pinned: 31 Dec '17

Vitamin D, Calcium, and Cardiovascular Disease: A"D"vantageous or "D"etrimental? An Era of Uncertainty.

Abstract: While the function of vitamin D in regulating calcium homeostasis is well established, there has been growing interest in its role in the prevention of numerous chronic diseases, including cardiovascular disease (CVD). There is mounting epidemiological evidence suggesting that vitamin D deficiency is linked to increased CVD risk. However, the results of previous vitamin D supplementation trials have yielded mixed results in regards to cardiovascular health, and the results of ongoing large-scale randomized controlled trials are not yet available. Further complicating the issue, calcium supplementation, which is often prescribed concurrently with vitamin D, has been associated with increased CVD risk in some (but not all) studies. Thus, it is currently unclear whether vitamin D supplements, particularly for those that are deficient, can help prevent the development of CVD. In addition, there has not been uniform consensus regarding the threshold of 25-hydroxyvitamin D levels that constitutes "sufficiency" across organizational guidelines. This review will provide an update on the most recent evidence regarding the effects of vitamin D and calcium supplements on CVD clinical outcomes, summarize ongoing vitamin D trials, and discuss the current but remarkably disparate recommendations regarding vitamin D deficiency screening and supplementation.

Pub.: 28 Jan '17, Pinned: 31 Dec '17

Relation of Epicardial Adipose Tissue Radiodensity to Coronary Artery Calcium on Cardiac Computed Tomography in Patients at High Risk for Cardiovascular Disease.

Abstract: Adipose tissue radiodensity detected by computed tomography (CT) is hypothesized to be associated with differences in adipose tissue composition which may contribute to the development of coronary atherosclerosis independent of epicardial adipose tissue volume. The aim of the present study is to quantify the relation between epicardial adipose tissue radiodensity and presence, distribution, and density of coronary artery calcium (CAC) in patients at high risk for cardiovascular disease. A total of 140 patients of the Secondary Manifestations of ARTerial disease (SMART) study underwent cardiac-CT angiography. Ordinal logistic and linear regression was used to quantify the relation between epicardial adipose tissue radiodensity (in Hounsfield Units, HU) and CAC. One SD lower attenuation (5 HU) was associated with a 1.90 (95% confidence interval [CI] 1.14 to 3.19) higher odds for men and a 1.07 (95% CI 0.41 to 2.75) higher odds for women of being in a higher CAC class (0, 1 to 100, 101 to 400, and >400), independent of age, coronary artery bypass graft history, epicardial adipose tissue volume, and body mass index. One SD lower attenuation was not associated with more diffuse distribution of CAC, but increased the odds of being in a higher tertile of CAC density per plaque (odds ratio 1.77, 95% CI 1.18 to 2.66). In conclusion, low epicardial adipose tissue CT attenuation is associated with higher CAC scores in men at high risk for cardiovascular disease, independent of epicardial depot volume and body mass index. Present results suggest a potential role for epicardial adipose tissue radiodensity as a measure of adipose tissue composition and may inform on the contribution of epicardial adipose tissue composition to coronary atherosclerosis.

Pub.: 11 Mar '17, Pinned: 31 Dec '17

The effect of increasing dairy calcium intake of adolescent girls on changes in body fat and weight.

Abstract: Background: Overweight is epidemic in adolescents and is a major concern because it tracks into adulthood. Evidence supports the efficacy of high-calcium, high-dairy diets in achieving healthy weight in adults. However, no randomized controlled trials of the effect of dairy food on weight and body fat in adolescents have been reported to our knowledge.Objective: The aim was to determine whether increasing calcium intake to recommended amounts with dairy foods in adolescent girls with habitually low calcium intakes would decrease body fat gain compared with girls who continued their low calcium intake. Participants had above-the-median body mass index (BMI; in kg/m(2)).Design: We enrolled 274 healthy postmenarcheal 13- to 14-y-old overweight girls who had calcium intakes of ≤600 mg/d in a 12-mo randomized controlled trial. Girls were randomly assigned in a 1:1 ratio to 1 of 2 groups within each of 3 BMI percentiles: 50th to <70th, 70th to <85th, and 85th to <98th. The assignments were 1) dairy, which included low-fat milk or yogurt servings providing ≥1200 mg Ca/d or 2) control, which included the usual diet of ≤600 mg Ca/d.Results: We failed to detect a statistically significant difference between groups in percentage of body fat gain over 12 mo (mean ± SEM: dairy 0.40% ± 0.53% > control; P < 0.45). The effect of the intervention did not differ by BMI percentile stratum. There was no difference in weight change between the 2 groups.Conclusion: Our findings that the dairy group gained body fat similar to the control group provide no support for dairy food as a stratagem to decrease body fat or weight gain in overweight adolescent girls. This trial was registered at clinicaltrials.gov as NCT01066806.

Pub.: 17 Mar '17, Pinned: 31 Dec '17

Dairy Food Intake and All-Cause, Cardiovascular Disease, and Cancer Mortality: The Golestan Cohort Study.

Abstract: We investigated the association between dairy product consumption and all-cause, cardiovascular disease (CVD), and cancer mortality in the Golestan Cohort Study, a prospective cohort study launched in January 2004 in Golestan Province, northeastern Iran. A total of 42,403 men and women participated in the study and completed a diet questionnaire at enrollment. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals. We documented 3,291 deaths (1,467 from CVD and 859 from cancer) during 11 years of follow-up (2004-2015). The highest quintile of total dairy product consumption (versus the lowest) was associated with 19% lower all-cause mortality risk (hazard ratio (HR) = 0.81, 95% confidence interval (CI): 0.72, 0.91; Ptrend = 0.006) and 28% lower CVD mortality risk (HR = 0.72, 95% CI: 0.60, 0.86; Ptrend = 0.005). High consumption of low-fat dairy food was associated with lower risk of all-cause (HR = 0.83, 95% CI: 0.73, 0.94; Ptrend = 0.002) and CVD (HR = 0.74, 95% CI: 0.61, 0.89; Ptrend = 0.001) mortality. We noted 11% lower all-cause mortality and 16% lower CVD mortality risk with high yogurt intake. Cheese intake was associated with 16% lower all-cause mortality and 26% lower CVD mortality risk. Higher intake of high-fat dairy food and milk was not associated with all-cause or CVD mortality. Neither intake of individual dairy products nor intake of total dairy products was significantly associated with overall cancer mortality. High consumption of dairy products, especially yogurt and cheese, may reduce the risk of overall and CVD mortality.

Pub.: 04 Apr '17, Pinned: 31 Dec '17

Dietary calcium intake and risk of cardiovascular disease, stroke, and fracture in a population with low calcium intake.

Abstract: Background: The role of dietary calcium intake in cardiovascular disease (CVD), stroke, and fracture is controversial. Most previous reports have evaluated populations with high calcium intake.Objective: We aimed to evaluate whether high dietary calcium intake was associated with the risk of CVD, stroke, and fracture in a population with low calcium intake.Design: In a prospective cohort study beginning in 2001 in Ansung-Ansan, Korea, 2158 men and 2153 women aged >50 y were evaluated for all-cause mortality, CVD, stroke, and fractures over a median 9-y follow-up.Results: During follow-up, 242 and 100 deaths, 149 and 150 CVD events, 58 and 82 stroke events, and 211 and 292 incident fractures occurred in men and women, respectively. The first quartiles of energy-adjusted dietary calcium intake were 249 mg/d (IQR: 169 mg/d) in men and 209 mg/d (IQR: 161 mg/d) in women. Both men and women with higher dietary calcium intake tended to have higher fat, protein, sodium, phosphorus, fruit, and vegetable intakes. In men, outcomes were not significantly associated with dietary calcium intake with or without adjustments, and CVD risk tended to increase with increasing energy-adjusted dietary calcium intake, but this was not statistically significant (P = 0.078 and P = 0.093 with and without adjustment, respectively). In women, CVD risk and dietary calcium intake showed a U-shaped association; the HRs (95% CIs) without adjustment relative to the first quartile were 0.71 (0.47, 1.07), 0.57 (0.36, 0.88), and 0.52 (0.33, 0.83) for quartiles 2, 3, and 4, respectively, and the values after adjustment were 0.70 (0.45, 1.07), 0.51 (0.31, 0.81), and 0.49 (0.29, 0.83) for quartiles 2, 3, and 4, respectively.Conclusion: In Korean women, increased dietary calcium intake was associated with a decreased CVD risk, but it did not influence the risk of stroke or fracture.

Pub.: 16 Jun '17, Pinned: 31 Dec '17

Independent associations of dairy and calcium intakes with colorectal cancers in the Adventist Health Study-2 cohort.

Abstract: Results associating dairy and Ca intakes with colorectal cancer (CRC) risk have been mixed. Most previous analyses have suffered from confounding between dairy and Ca intakes. We examined independent associations between these variables, also dairy foods, and CRC incidence in a population with a large range of dairy intakes.Adventist Health Study-2 is a cohort study where subjects were enrolled 2002-2007. Proportional hazard regression analyses were performed to estimate hazard ratios (HR). Regression calibration was used to correct for dietary measurement error.The population lived in all states of the USA.There were 77712 analytic subjects, all of whom were Seventh-day Adventists. Much of their dietary Ca came from non-dairy sources.During a mean follow-up of 7·8 years, 380 incident colon cancer and 111 incident rectal cancer cases were observed.Comparing extreme quintiles of intake in measurement error-corrected analyses, dairy intake (HR=0·31; 95 % CI 0·09, 0·88), independent of total Ca, was inversely related with risk of rectal cancer but gave little indication of association with colon cancer. However, total Ca intake (independent of dairy) was associated with risk of colon cancer (HR=0·55; 95 % CI 0·28, 0·98) and there was little indication of association with rectal cancer. Traditional regression analyses and associations with macronutrients from dairy generally supported these results. Milk intake was also negatively associated with CRC (HR=0·63; 95 % CI 0·43, 0·89).Dairy intake may decrease the risk of rectal cancer, and Ca may reduce risk of colon cancer and CRC.

Pub.: 25 Jul '17, Pinned: 31 Dec '17

Association of cardiovascular disease risk factors with coronary artery calcium volume versus density.

Abstract: Recently, the density score of coronary artery calcium (CAC) has been shown to be associated with a lower risk of cardiovascular disease (CVD) events at any level of CAC volume. Whether risk factors for CAC volume and CAC density are similar or distinct is unknown. We sought to evaluate the associations of CVD risk factors with CAC volume and CAC density scores.Baseline measurements from 6814 participants free of clinical CVD were collected for the Multi-Ethnic Study of Atherosclerosis. Participants with detectable CAC (n=3398) were evaluated for this study. Multivariable linear regression models were used to evaluate independent associations of CVD risk factors with CAC volume and CAC density scores.Whereas most CVD risk factors were associated with higher CAC volume scores, many risk factors were associated with lower CAC density scores. For example, diabetes was associated with a higher natural logarithm (ln) transformed CAC volume score (standardised β=0.44 (95% CI 0.31 to 0.58) ln-units) but a lower CAC density score (β=-0.07 (-0.12 to -0.02) density units). Chinese, African-American and Hispanic race/ethnicity were each associated with lower ln CAC volume scores (β=-0.62 (-0.83to -0.41), -0.52 (-0.64 to -0.39) and -0.40 (-0.55 to -0.26) ln-units, respectively) and higher CAC density scores (β= 0.41 (0.34 to 0.47), 0.18 (0.12 to 0.23) and 0.21 (0.15 to 0.26) density units, respectively) relative to non-Hispanic White.In a cohort free of clinical CVD, CVD risk factors are differentially associated with CAC volume and density scores, with many CVD risk factors inversely associated with the CAC density score after controlling for the CAC volume score. These findings suggest complex associations between CVD risk factors and these components of CAC.

Pub.: 18 Aug '17, Pinned: 31 Dec '17

Calcium and Cardiovascular Disease.

Abstract: Circulating calcium is a risk factor for vascular disease, a conclusion arising from prospective studies involving hundreds of thousands of participants and extending over periods of up to 30 years. These associations may be partially mediated by other cardiovascular risk factors such as circulating lipid levels, blood pressure, and body mass index, but there appears to be a residual independent effect of serum calcium. Polymorphisms of the calcium-sensing receptor associated with small elevations of serum calcium are also associated with cardiovascular disease, suggesting that calcium plays a causative role. Trials of calcium supplements in patients on dialysis and those with less severe renal failure demonstrate increased mortality and/or acceleration of vascular disease, and meta-analyses of trials in those without overt renal disease suggest a similar adverse effect. Interpretation of the latter trials is complicated by a significant interaction between baseline use of calcium supplements and the effect of randomisation to calcium in the largest trial. Restriction of analysis to those who are calcium-naive demonstrates a consistent adverse effect. Observational studies of dietary calcium do not demonstrate a consistent adverse effect on cardiovascular health, though very high or very low intakes may be deleterious. Thus, obtaining calcium from the diet rather than supplements is to be encouraged.

Pub.: 29 Sep '17, Pinned: 31 Dec '17

Associations of Calcium and Dairy Products with All-Cause and Cause-Specific Mortality in the REasons for Geographic and Racial Differences in Stroke (REGARDS) Prospective Cohort Study.

Abstract: Associations of calcium and dairy product intakes with cardiovascular disease risk and cancer mortality are controversial. We investigated associations of calcium and dairy product intakes with mortality in the prospective REasons for Geographic and Racial Differences in Stroke study (n = 30,239). Of 2,966 total deaths, 32.3% were from CVD and 28.8% from cancer. For those in the upper relative to the lowest quintile of intakes, from Cox proportional hazards regression models, the multivariable-adjusted hazard ratios (HRs) for all-cause mortality were 1.13 (95% confidence intervals [CI] 0.95-1.35; P-trend 0.004) for whole milk, and 0.75 (CI 0.61-0.93; P-trend 0.001) for nonfat milk; for CVD mortality the corresponding HRs were 0.80 (CI 0.55-1.16; P-trend 0.80) and 0.72 (CI 0.49-1.05; P-trend 0.06); and for cancer mortality they were 1.56 (CI 1.17-2.08; P-trend 0.006) and 0.89 (CI 0.62-1.28; P-trend 0.86). Calcium (total, dietary, supplemental) and total dairy product intakes were not associated with all-cause, cardiovascular, or cancer mortality. These results suggest that whole milk consumption may be directly associated with cancer mortality; non-fat milk consumption may be inversely associated with all-cause and cardiovascular- and cancer-specific mortality; and calcium intake independent of milk product intakes may not be associated with mortality.

Pub.: 11 Nov '17, Pinned: 31 Dec '17

Influence of dairy product and milk fat consumption on cardiovascular disease risk: a review of the evidence.

Abstract: Although evidence has linked the consumption of saturated fat (SF) to increased LDL levels and an increased risk of the development of cardiovascular disease (CVD), recent findings have indicated that the link between CVD and SF may be less straightforward than originally thought. This may be due to the fact that some food sources high in SF contain an array of saturated and unsaturated fatty acids, each of which may differentially affect lipoprotein metabolism, as well as contribute significant amounts of other nutrients, which may alter CVD risk. The purpose of this review is to examine the published research on the relationship between milk fat containing dairy foods and cardiovascular health. The findings indicate that the majority of observational studies have failed to find an association between the intake of dairy products and increased risk of CVD, coronary heart disease, and stroke, regardless of milk fat levels. Results from short-term intervention studies on CVD biomarkers have indicated that a diet higher in SF from whole milk and butter increases LDL cholesterol when substituted for carbohydrates or unsaturated fatty acids; however, they may also increase HDL and therefore might not affect or even lower the total cholesterol:HDL cholesterol ratio. The results from the review also indicate that cheese intake lowers LDL cholesterol compared with butter of equal milk fat content. In addition, the review highlights some significant gaps in the research surrounding the effects of full-fat dairy on CVD outcomes, pointing to the need for long-term intervention studies.

Pub.: 16 May '12, Pinned: 31 Dec '17