Nutrition Updates


  • Kris D'Anci


Sacks FM, Bray GA, Carey VJ, Smith SR, Ryan DH, Anton SD, McManus K, Champagne CM, Bishop LM, Laranjo N, Leboff MS, Rood JC, de Jonge L, Greenway FL, Loria CM, Obarzanek E, and Williamson DA. Comparison of weight-loss diets with different compositions of fat, protein, and carbohydrates. N Engl J Med. 2009;360:859–873.

In the popular press, many diets espouse the notion that heavily favoring one macronutrient profile over others will provide the most effective weight loss. In recent years, the low-fat, high-carbohydrate mantra has been supplanted by the low-carbohydrate, high-fat and -protein craze. Many individuals hoping to lose a significant amount of weight will follow a new and popular diet with enthusiasm and can lose weight in the short term. Long-term weight loss, however, remains elusive for the majority of dieters. Many studies have evaluated the efficacy of weight-loss diets with differing macronutrient content on short-term weight loss, but few of these studies extend beyond 1 year. In the present trial, Sacks et al. assigned overweight individuals to different diet conditions and provided extensive group and individual support and guidance for 2 years.

Eight-hundred and eleven participants (515 women) with BMIs between 25 and 40 were randomly assigned to one of four dietary conditions: Low-fat, average-protein; low-fat, high-protein; high-fat, average-protein; high-fat, high-protein. All diets met current guidelines for cardiovascular health and provided between 35% and 65% carbohydrate. Diets could not contain more than 8% of energy from saturated fats, no more than 150 mg cholesterol/1000 kCal, and they needed to contain a minimum of 20 g dietary fiber. Each participant received a caloric prescription based on a 750 kCal deficit per day from baseline intake. Behavioral counseling was integrated into group and individual sessions over the 2-year trial. Physical activity goals of 90 min/week were set for all participants. The primary outcome of the trial was change in body weight over a period of 2 years. Secondary outcomes included change in waist circumference, and changes in serum lipids, insulin, glucose, and glycated hemoglobin. Weight losses over time were similar for each diet condition, and peaked with 6 kg losses at 6 months. After 12 months, although still assigned to calorie restriction, participants began to regain weight and final losses at 2 years averaged 4% in all groups. Within the diet conditions, attendance at group sessions was associated with the greatest weight loss (0.2 kg loss per session attended). All of the reduced calorie diets produced reductions in risk factors for cardiovascular disease and diabetes at 6 months and 2 years. After 2 years, the low-fat diets and the highest carbohydrate diet reduced LDL-cholesterol levels to a greater degree than the high-fat diets or the lowest carbohydrate diet. All diets, with the exception of the highest carbohydrate diet, decreased insulin levels. The present trial suggests that calorie reduction rather than macronutrient manipulation can result in clinically meaningful weight loss. Choosing a particular macronutrient formula for a diet may be more important if risk factors for cardiovascular disease or diabetes are present. Finally, the most important predictor of successful weight loss was participation in the behavioral support meetings, which was associated with greater dietary compliance and may serve as a proxy for commitment to a weight-loss program.

Comment: Dr. Katan acknowledges the difficulty inherent in long-term weight-loss trials. In the current report, highly motivated researchers and highly motivated participants were unable to sustain target macronutrient intake and weight loss. The participants who were most engaged in the behavioral support sessions were the most successful over the 2 years of the trial. Thus far, the best dietary intervention weight-loss trials suggest that individuals will average a 3–4 kg weight loss over 2–4 years, and these losses will be attenuated in those that are very overweight, poor, or unmotivated. Dr. Katan argues that a shift towards a total-environment approach, including community involvement and community action, is needed in the effort to prevent obesity.

Comment: Katan MB. Weight-loss diets for the prevention and treatment of obesity. N Engl J Med. 2009;360:923–925.


Molloy AM, Kirke PN, Troendle JF, Burke H, Sutton M, Brody LC, Scott JM, and Mills JL. Maternal vitamin B12 status and risk of neural tube defects in a population with high neural tube defect prevalence and no folic acid fortification. Pediatrics. 2009;123:917–923.

In recent years, several countries have implemented mandatory fortification of grain products with folic acid, with the primary goal of reducing the incidence of neural tube defects. Fortification has been successful at reducing neural tube defects by 35–78%, and there is some question remaining as to whether all folic acid-preventable neural tube defects are being addressed or whether neural tube defects from other causes comprise the remainder. There has been some discussion of whether to raise fortification levels, but the possibilities that high-dose folic acid may not be universally beneficial (see the report from Figueiredo et al., below) and that not all neural tube defects are attributable to low folate status make this avenue unlikely. It behooves us, therefore, to determine other factors affecting proper development of the neural tube during pregnancy. Vitamin B12, like folate, is an important component of one-carbon metabolism, which is crucial for DNA synthesis and methylation reactions, perturbations of which can affect embryonic development. Molloy et al. examine the role of vitamin B12 status in pregnancies affected by neural tube defects in a population of women with no folic acid fortification.

Blood samples from three groups of women (N = 1179) were analyzed for serum B12 and folate levels and also for red blood cell folate levels. Each group of women included those with pregnancies affected by neural tube defects and case controls. All participants lived in Ireland and samples were drawn between 1983 and 1990. Group 1 consisted of women with current pregnancies affected by neural tube defects during 1983–1986. Group 2 consisted of women with a previous neural tube defect pregnancy, but whose current pregnancy during 1986–1990was not affected. Group 3 was similar to group 1 but the samples were drawn during 1986–1990. In all three groups, vitamin B12 concentrations <250 ng/L had a 2.5- to 3.0-fold higher risk of having a pregnancy affected by a neural tube defect independent of folate status. Those with B12 concentrations <150 ng/L had 5-fold higher risk for an affected pregnancy relative to those with B12 values >400 ng/L. Independent of folate, each unit increase of vitamin B12 was associated with a 0.3% reduction in risk for an affected pregnancy. The authors indicate that those with vitamin B12 concentrations below 300 ng/L during pregnancy are at significantly higher risk for neural tube defects in their offspring. These data are limited to B12 values during pregnancy; however, as little is known about the relationship between pre-pregnancy B12 status and neural tube defects. The present findings support the notion that focusing on fortification with folic acid alone is insufficient to address the public health risk for developing neural tube defects.


Figueiredo JC, Grau MV, Haile RW, Sandler RS, Summers RW, Bresalier RS, Burke CA, McKeown-Eyssen GE, and Baron JA. Folic acid and risk of prostate cancer: results from a randomized clinical trial. J Natl Cancer Inst. 2009;101:432–435.

High dietary levels of folate are associated with reduced risk for cancer. However, recent evidence indicates that high-dose folic acid supplementation may increase the risk for colorectal cancer, although the role of high-dose folic acid in other cancers is less well studied. The present communication from Figueiredo et al. reports on the risk for prostate cancer following long-term supplementation of 1 mg/d folic acid.

The study, which is a secondary analysis of the Aspirin/Folate Polyp Prevention Study, follows 643 men over a period of up to 10.8 years of supplement use. In the original trial, participants were randomized to receive 1.0 mg/d folic acid or placebo and aspirin (81 or 325 mg/d) or placebo. All participants completed semiquantitative food frequency questionnaires and provided blood samples to be assayed for baseline folate and other B vitamins. Aspirin had no effect on prostate cancer incidence. For those taking the folic acid supplement, the estimated probability of developing prostate cancer was 9.7%, in comparison to a 3.3% probability in the placebo group. Among those men not taking vitamins, there was an inverse relationship between folate levels and risk of prostate cancer. The opposing effects of natural folates and the synthetic analogue folic acid on prostate cancer risk may be related to their differing structure, metabolic intermediaries, and bioavailability. There were relatively low levels of prostate cancer in this analysis, and the original study outcome was prevention of colorectal adenomas, so the present study may be underpowered. However, the authors indicate that the present data highlight the importance of differentiating the effects of folate from natural sources in comparison to folic acid in the risk for cancer.


St-Onge MP, Zhang S, Darnell B, and Alison DB. Baseline serum C-reactive protein is associated with lipid responses to low-fat and high-polyunsaturated fat diets. J Nutr. 2009;139:680–683.

High-sensitivity C-reactive protein (CRP) is an indicator of inflammation and a marker for cardiovascular disease risk. In particular, baseline CRP may be useful in predicting lipid response following intake of different diets. Such differences could have important implications in dietary recommendations to maintain cardiovascular health. St-Onge et al. report on a randomized, crossover study that examined the relationship between baseline CRP levels and lipid responses to diets with differing levels and types of fat.

Thirty-three participants (26 women) completed the study, which consisted of three phases of controlled feeding (25 days each) separated by 4–8 weeks of washout. Each participant completed each phase of the trial. The main diet in each phase was the same; however snacks differed in fat type and fat content, i.e., low-fat; moderate fat with high PUFA; and moderate-fat with high saturated fat and trans fat (referred to as a Western diet). The low-fat diet contained ∼30% fat and the moderate-fat diets contained ∼37% fat. Blood samples were collected at baseline and throughout the phases of the study. In addition to CRP, serum levels of total cholesterol, HDL- and LDL-cholesterol, triglycerides, and lipoprotein were measured. CRP levels were classified into low, moderate, and high, and baseline levels were compared with all outcome variables; data were also analyzed with CRP as a continuous variable. In individuals with moderate or high CRP values at baseline, triglycerides increased with the low-fat diet relative to the Western diet. In those with high CRP at baseline, triglycerides decreased with the high-PUFA diet relative to the Western diet. Overall, the high-PUFA diet tended to lower LDL-cholesterol relative to the Western diet. The low-fat diet reduced LDL-cholesterol in those with low or moderate baseline CRP values, but not in those with high CRP values. The authors suggest that baseline CRP levels should be taken into consideration when designing dietary interventions to lower blood lipids. Those with high CRP levels may benefit more from moderate-fat high-PUFA diets and those with low CRP levels may obtain greater benefit from traditional low-fat diets.


Tucker KL, Jugdaohsingh R, Powell JJ, Qiao N, Hannan MT, Sripanyakorn S, Cupples LA, and Kiel DP. Effects of beer, wine, and liquor intakes on bone mineral density in older men and women. Am J Clin Nutr. 2009 doi:10.3945/ajcn.2008.26765

Moderate intake of alcoholic beverages has been reported to be protective against bone loss in older women. Data in men and in younger women is relatively lacking. Additionally, few studies have distinguished between never drinkers and former drinkers. This raises the possibility that former drinkers, who may have lower bone mineral density due to alcohol abuse or illness, may bias the data in favor of moderate alcohol intake for bone health. Tucker et al. analyzed alcohol intake and bone mineral density in the Framingham Offspring cohort (N = 2719; 1537 women).

Alcohol intakes were assessed using a food frequency questionnaire and were categorized into 0, 0–0.5, 0.5–1, 1–2, and >2 drinks/d. Alcohol intake was further differentiated by type as wine, beer, or hard alcohol. Bone mineral densities from the lumbar spine, total hip, trochanter, and femoral neck were compared across intake categories. In the present analysis, there were no differences in bone mineral density between never drinkers and former drinkers. Beer was most commonly consumed among men, and wine was more commonly consumed among women. Bone mineral density was lower in those drinking <0.05 drink/d relative to those drinking 1–2 drinks/d. Bone mineral density was lowest in men drinking more than 2 drinks/d. For beer drinkers, adjustment for silicon intake eliminated the effects of beer on bone mineral density. In postmenopausal women, alcohol intake was linearly associated with bone mineral density, with the lowest bone mineral density seen in those drinking <0.5 drink/d and the highest bone mineral density seen in those drinking more than 2 drinks/d. No associations were seen in premenopausal women, but the authors indicate that the study's power was too low to detect any meaningful relationship. Moderate intake (1–2 drinks/d) of wine and beer appear to be protective in preserving bone mineral density in older men and women. This relationship was less robust for hard liquor, suggesting that other components of beer (i.e. silicon) and wine (i.e. resveratrol) may be responsible for the primary outcomes on bone health.

Comment: In a related editorial, Dr. Macdonald raises the important observation that current servings of alcoholic beverages have increased relative to the standard sizes used in most reports on alcohol intake, and that it is likely that there is underreporting of true alcohol intake. While this observation does not negate the associations between moderate alcohol intake and bone health, it does elucidate the need for caution in recommending how much alcohol to consume. She also suggests that if it is not ethanol per se that is responsible for mediating bone mineral density in older individuals, then other foods containing similar nutrients could also be recommended for the maintenance of bone mineral density.

Comment: Macdonald HM. Alcohol and recommendations for bone health: should we still exercise caution? Am J Clin Nutr. 2009 doi:10.3945/ajcn.2009.27574