GENETIC DISCLOSURE ON APOE GENOTYPE STATUS INFLUENCES SUPPLEMENT USE
Vernarelli JA, Roberts JS, Hiraki S, Chen CA, Cupples LA, and Green RC. Effect of Alzheimer's disease genetic risk disclosure on dietary supplement use. Am J Clin Nutr. 2010;91:1402–1407.
With a greater understanding of the human genome has come the advent of direct-to-consumer (DTC) genetic testing. Use of these widely available tests is controversial as they are not well-regulated and can be highly variable. One difficulty in interpreting information from genetic tests is that while mutations in certain genes are associated with increased risk for an illness, these mutations are very seldom causative in ontogeny of disease. Nevertheless, individuals use risk information to make behavior changes and companies use genetic risk information to market supplements and nutraceuticals offering protection or risk-reduction for a disease. Vernarelli et al. examine the extent to which disclosure of Alzheimer's disease genetic risk affects dietary supplement use.
The development of Alzheimer's disease depends on both genetic and nongenetic factors. There are several susceptibility genes associated with Alzheimer's disease, including the APOE gene, which has three variants. Individuals with the APOE ε4 variant have an increased risk for developing Alzheimer's disease, but this risk can be modified by other factors including sex, age, and race. Previous work shows that individuals with the APOE ε4 variant and a family history of Alzheimer's disease are more likely to make health-behavior changes than those without the APOE ε4 variant. The present data are a secondary analysis from the second Risk Evaluation and Education for Alzheimer's Disease (REVEAL II) Study.
Participants (n = 272) were enrolled into REVEAL II between 2003 and 2005. Individuals were eligible for the study if they were cognitively intact and had a first-degree relative with Alzheimer's disease. Participants were given information about APOE variant status and were provided with an age-adjusted lifetime risk of developing Alzheimer's based on genotype, sex, and ethnicity. Six weeks after disclosure, participants were questioned on health-behavior changes, including dietary and supplement changes, made since learning their genotype status. Individuals who learned they had at least one copy of the ε4 allele were significantly more likely to report a change in dietary supplement use than those without the ε4 allele. There was no effect of allele type on other behaviors such as diet or exercise. The majority of participants reported multivitamin or single-vitamin supplement use, 25% reported using a combination of vitamins and botanicals. The most commonly consumed supplements included vitamin E, vitamin C, vitamin B, fish oil, and botanicals such as gingko biloba, green tea, and curcumin. Participants initiated supplement use despite a lack of information that such supplements reduce the risk of developing Alzheimer's disease. The authors suggest that these data show a need for further studies in disease risk communication.
Comment: Drs. Dwyer and Donoghue underscore the limitations and hazards of relying on genotyping to determine disease risk. For example, individuals without the ε4 allele but with other risk factors such as family history of early-onset Alzheimer's disease are at increased risk for Alzheimer's. Since the evidence shows that individuals will make health-related changes following disclosure of risk, it is incumbent upon health professionals to provide counseling on the types of behavior change that are likely to provide a benefit as well as those that are less useful for health maintenance.
Comment: Dwyer J and Donoghue MD. Is risk of Alzheimer disease a reason to use dietary supplements? Am J Clin Nutr. 2010; 91:1155–1156.
POTENTIAL IMPACT OF DECREASED SODIUM INTAKE ON CARDIOVASCULAR DISEASE
Smith-Spangler CM, Juusola JL, Enns EA, Owens DK, and Garber AM. Population strategies to decrease sodium intake and the burden of cardiovascular disease: A cost-effectiveness analysis. Ann Intern Med. 201;152:481–487.
Excess sodium in the diet is linked with increased blood pressure and increased risk for heart attack and stroke. Over the past 40 years, government agencies and organizations for health professionals have endeavored to reduce the consumption of excess sodium in the US population, but these efforts have been largely unsuccessful. In April 2010, the Institute of Medicine Food and Nutrition Board recommended standards and strategies that food manufacturers should use to reduce the amount of sodium in processed foods. The majority of sodium in the diet comes not from salt added during food preparation and at the table, but rather in the manufacture of prepared and processed foods. Adequate sodium intake for healthy physiological functioning is currently estimated to be 1,500 mg/day. Americans consume, on average, over 3,400 mg of sodium daily, which is more than twice the adequate amount and well above the recommended upper limit of 2,300 mg/day (or the upper limit of 1,500 mg/day for individuals with hypertension, African Americans, and people over the age of 40 years). In the current report, Smith-Spangler et al. present a cost-effectiveness analysis for using population-wide strategies to decrease sodium intake.
Recent efforts in the United Kingdom have been successful at reducing sodium intakes in the population. Food safety agencies worked in conjunction with food manufacturers to cut sodium by developing maximum sodium targets for specific foods. Decreases in added sodium in the United Kingdom led to an estimated 9.5% decrease in population sodium intake. In the analysis, Smith-Spangler et al. generated a computer-simulated model of incidence, prevalence, mortality, and direct costs associated with stroke and myocardial infarction in US adults aged 40–85 years. Record sources covered data from the Medical Panel Expenditure Survey (2006), the Framingham Heart Study (1980–2003), and the Dietary Approaches to Stop Hypertension (DASH) trial. Outcome measures included incremental healthcare costs, quality-adjusted life-years, and averted stroke or myocardial infarction. Using an estimated 9.5% decrease in population sodium intake, taken from the United Kingdom estimate data, strategies aimed at decreasing sodium intake could prevent 513,885 strokes and 480,385 cases of myocardial infarction over the lifetime of currently living adults. Based on these projections, the United States could see an estimated $32.1 billion reduction in healthcare costs and an increase of 2.1 million quality-adjusted life-years. A second analysis modeling the effects of a tax on sodium producing a 6% decrease in population sodium intake increases quality-adjusted life-years by 1.3 million and saves $22.4 billion in healthcare costs. Limitations and considerations with this type of analysis include the assumption that people have no issues with modest reductions in sodium in prepared foods and that decreases in sodium do not lead to other dietary changes that can affect cardiovascular disease risk. The authors conclude that implementing strategies such as reduced use of sodium in food manufacture and taxes on sodium could substantially reduce the incidence of stroke and heart attack as well as reduce the economic burden associated with cardiovascular disease.
Comment: Drs. Frieden and Briss support the proposal that policy changes in food manufacturing may have a significant impact on US public health. While present efforts to assist individuals in reducing sodium intake can be useful, population-wide changes in the sodium content of foods are a more efficient means of impacting the health of large numbers of people. They argue, however, that taxation of salt, which is both inexpensive and ubiquitous, may not lead to significant reductions in intake. Instead, they suggest point-of-purchase package labeling might be an effective complimentary strategy to help individuals make informed choices.
Frieden TR and Briss PA. We can reduce dietary sodium, save money, and save lives. Ann Intern Med. 2010;152:526–527.
DIETARY B6 AND FOLATE ASSOCIATED WITH REDUCED MORTALITY IN CARDIOVASCULAR DISEASE
Cui R, Iso H, Date C, Kikuchi S, and Tamakoshi A; for the Japan Collaborative Cohort Study Group. Dietary folate and vitamin B6 and B12 intake in relation to mortality from cardiovascular diseases. Japan Collaborative Cohort Study. Stroke. 2010; published online April 15, 2010. doi: 10.1161/STROKEAHA.110.578906
The association between high blood concentrations of homocysteine and cardiovascular disease has been widely reported. Vitamins B6, B12, and folate are critical cofactors in homocysteine metabolism, and high dietary intake of or supplementation with these nutrients lowers homocysteine. However, homocysteine-lowering protocols have been largely unsuccessful at ameliorating disease associated with high homocysteine levels. In Western populations, diets high in B vitamins are associated with reduced risk for stroke and cardiovascular disease and lower levels of homocysteine, but these associations have been explored to a lesser degree in Asian populations. Cui et al. report on associations between dietary B vitamin intake and cardiovascular mortality using data from the Japanese Collaborative Cohort Study.
Data collection for this study began between 1988 and 1990, and follow-up data were collected through 1999–2003. The data analyzed in this report represent a subset of the original cohort that was free of cancer and cardiovascular disease at the beginning of the study. Food frequency data were available for men (n = 23,119) and women (n = 35,611) between the ages of 40 and 79 years. The main outcome measure in the present analysis was death related to cardiovascular disease, including stroke. Over the median 14-year follow-up period, there were 2,087 deaths from cardiovascular disease, 424 deaths from coronary heart disease, and 986 deaths from stroke. In men, there was an inverse relationship between folate and vitamin B6 intake and mortality from heart failure. In women, vitamin B6 and folate intakes were inversely related to deaths from stroke, coronary heart disease, and cardiovascular disease. These differences remained significant after excluding individuals who used multivitamin supplements (n = 7,334). There was no relationship between vitamin B12 intake and mortality. These data are consistent with observations on the relationship between dietary folate and vitamin B6 intake and cardiovascular disease in Western populations and the first to reflect a reduced risk for heart failure in men. One weakness in interpreting the present data is the lack of available data on homocysteine or other markers for cardiovascular disease in the study population. Additionally, individuals who had higher intake of B vitamins had higher intake of fish and lower history of hypertension. However, the observed relationships between B vitamin intake and reduced mortality were still evident after controlling for potential confounds and after excluding multivitamin users. These findings further underscore the importance of diets rich in folate and vitamin B6 in reducing the risk of death from cardiovascular- and cerebrovascular-related events.
RELATIONSHIP BETWEEN ADIPOSITY AND VITAMIN K STATUS
Shea MK, Booth SL, Gundberg CM, Peterson JW, Waddell C, Dawson-Hughes B, and Saltzman E. Adulthood obesity is positively associated with adipose tissue concentrations of vitamin K and inversely associated with circulating indicators of vitamin K status in men and women. J Nutr. 2010;140:1029–1034.
The fat-soluble vitamins A, D, and E are concentrated and stored in adipose tissue. It has been proposed that individuals who are overweight or obese may have increased storage of fat-soluble vitamins and decreased circulating levels of these vitamins. As an example, some research shows that low vitamin D status in obesity is related to vitamin D storage in adipose tissue, which limits its bioavailability. Relatively little is known about the relationship between vitamin K availability and adiposity. It is reasonable to hypothesize that vitamin K sequestering in fat tissue and reduced circulating levels would be similar to that of the other fat-soluble vitamins, but until now this has not been examined directly. Shea et al. report on two studies describing 1) the extent to which vitamin K is stored in adipose tissue, and 2) the association between circulating vitamin K and body fat in older men and women.
In the first study, obese individuals (N = 16; 13 females) undergoing gastric bypass surgery consented to have their blood and tissue sampled and analyzed for vitamin K concentrations. Blood draws were taken 1–2 weeks prior to scheduled surgery. Abdominal subcutaneous and visceral adipose tissue samples were collected at the time of surgery. Plasma and adipose tissue concentrations of phylloquinone (K1 ), menaquinone-4 (MK-4), and dihydrophylloquinone (DK1) were measured using high-performance liquid chromatography. High concentrations of K1 were seen in adipose tissue, and MK-4 and DK1 were also present to a lesser degree. The authors indicate that K1 may accumulate in adipose tissue to a greater degree than in other human organs.
In the second study, 443 participants (260 female) between the ages of 60 and 80 years were recruited into a trial examining the impact of vitamin K supplementation on age-related bone loss. The data for the present paper represent a secondary, cross-sectional analysis of vitamin K status determined using baseline fasting blood draws. Vitamin K status was analyzed in relationship to percent body fat. Percent body fat ranged from 15.2% to 50% in women and from 10.7% to 45.7% in men. Plasma levels of vitamin K were inversely related to percent body fat in women but not in men, although none of the subjects were vitamin K deficient. For both men and women, a higher percentage of body fat was associated with higher circulating levels of the clotting factor prothrombin, suggesting a lower hepatic utilization of vitamin K. The present study is the first to report on vitamin K status in relationship to body fatness. The data suggest that vitamin K may be stored in high concentrations in adipose tissue, and, in overweight women, this may result in a lower vitamin K status relative to leaner women.
EXTRA-VIRGIN OLIVE OIL REPRESSES EXPRESSION OF PRO-INFLAMMATORY GENES
Camargo A, Ruano J, Fernandez JM, Parnell LD, Jimenez A, Santos-Gonzalez M, Marin C, Perez-Martinez P, Uceda M, Lopez-Miranda J, and Perez-Jimenez F. Gene expression changes in mononuclear cells from patients with metabolic syndrome after acute intake of phenol-rich virgin olive oil. BMC Genomics. 2010; doi:10.1186/1471-2164-11-253
The traditional Mediterranean diet is high in plant phenols, including olive oil. Individuals following a traditional Mediterranean diet are at reduced risk for cardiovascular disease, cognitive decline, and type 2 diabetes. It has been proposed that following a traditional Mediterranean diet may reduce risk for disease progression in at-risk individuals, such as people with metabolic syndrome, perhaps by reducing inflammation and oxidative stress. In vitro studies have shown that olive oil modifies gene expression coding for proteins involved in oxidative stress and lipid metabolism. Additionally, high-phenol virgin olive oil reduces pro-inflammatory, pro-oxidant, and pro-thrombotic markers compared with low-phenol oils, but the in vivo effects of olive oil on gene expression for these markers are not well understood. In the present study, Camargo et al. identify changes in gene expression mediated by virgin olive oil phenol compounds in humans.
Twenty men (n = 9) and women (n = 11) between the ages of 40 and 70 years with metabolic syndrome were randomized into the trial. During a 6-week washout period, participants were instructed to avoid the use of medications and supplements. For the duration of the study, all subjects followed a low-fat, carbohydrate-rich diet. Twenty-four hours prior to each breakfast intervention, participants were instructed to avoid consuming phenol-rich foods such as fruit or juices, olive oil, or soy, and to refrain from intense physical activity. Participants were assigned to a randomized sequential crossover design and given one of two breakfasts. After a 1-week washout period, participants received the other breakfast. The breakfast meals consisted of white bread (60G) and 40 mL of olive oil with either high (398 ppm) or low (70 ppm) phenolic content. Blood samples were obtained at 0, 30, 60, 120 and 240 min after consumption of each breakfast type. Microarray analysis of blood samples identified 98 differentially expressed genes when comparing the two types of olive oil. Relative expression of genes related to obesity, dyslipidemia, type 2 diabetes, and inflammatory processes was reduced following intake of the high-phenolic-content oil relative to the low-phenolic-content oil. The authors indicate that while a number of mitigating factors contribute to the progression of disease in individuals with metabolic syndrome, the present data show support for the molecular basis of phenol-rich foods in protection against inflammation and oxidative stress in humans.
DIETARY ADDED SUGARS ASSOCIATED WITH DYSLIPIDEMIA
Welsh JA, Sharma A, Abramson JL, Vaccarino V, Gillespie C, and Vos MB. Caloric sweetener consumption and dyslipidemia among US adults. JAMA. 2010;303:1490–1497.
High intake of dietary carbohydrates is associated with lower levels of high-density lipoprotein cholesterol and higher levels of low-density lipoprotein cholesterol and triglycerides. Dyslipidemia is associated with increased risk for cardiovascular disease. Although dietary carbohydrates are important for physical and mental functioning, recent scrutiny has been cast upon added sugars in the diet. Some estimates suggest that Americans over the age of 2 years consume nearly 16% of daily energy as added sugars. Recommendations on limits for added sugar intake vary from approximately 5% of total caloric intake (American Heart Association) to 25% (Institute of Medicine). Added sugars represent a potentially modifiable component in the diet to help reduce the risk for dyslipidemia. Welsh et al. examined the relationship between intake of added sugars and blood lipid levels in the US population.
Data were extracted from the National Health and Nutrition Examination Survey (NHANES) 1999–2006. Individuals were included in the analysis if they had available fasting blood samples, were free from diabetes, not using cholesterol-lowering medication, and were not pregnant. The final analysis reported here includes data from 6,113 adults (3,088 women) over the age of 18 years. Food intake was determined using a 24-hour dietary recall (an average of two recalls were used, if available), and nutrient content of foods was determined by NHANES using the Food and Nutrient Database for Dietary Studies. Information on added sugars was estimated using the MyPyramid Equivalents Database files and from manufacturer-provided nutrition label information. Added sugar intake was categorized according to percent energy from added sugar: <5%; 5–≤10%; 10–≤17.5%; 17.5–≤25%; and ≥25%. Primary outcome measures included high-density-lipoprotein cholesterol, low-density-lipoprotein cholesterol, and triglycerides. The overall average intake of added sugars was 15.8% of total calories. Individuals consuming higher levels of added sugars were more likely to be younger, non-Hispanic black, and to have a low income. Intake of sugar was positively correlated with cigarette use and negatively correlated with hypertension. Self-reported weight gain in the year preceding the survey was higher in those reporting higher sugar intakes. High-density-lipoprotein cholesterol levels were inversely related to added sugar intake, and low-density-lipoprotein cholesterol and triglycerides were positively related to added sugar intake. The present data show a statistically significant association between dietary added sugars and dyslipidemia in the US adult population. The authors suggest that targeting a reduction in the intake of added sugars may be useful in modifying the risk for dyslipidemia.