Theodore J. Angelopoulos

Sucrose, High-Fructose Corn Syrup, and Fructose, Their Metabolism and Potential Health Effects: What Do We Really Know?

Both controversy and confusion exist concerning fructose, sucrose, and high-fructose corn syrup (HFCS) with respect to their metabolism and health effects. These concerns have often been fueled by speculation based on limited data or animal studies. In retrospect, recent controversies arose when a scientific commentary was published suggesting a possible unique link between HFCS consumption and obesity. Since then, a broad scientific consensus has emerged that there are no metabolic or endocrine response differences between HFCS and sucrose related to obesity or any other adverse health outcome. This equivalence is not surprising given that both of these sugars contain approximately equal amounts of fructose and glucose, contain the same number of calories, possess the same level of sweetness, and are absorbed identically through the gastrointestinal tract. Research comparing pure fructose with pure glucose, although interesting from a scientific point of view, has limited application to human nutrition given that neither is consumed to an appreciable degree in isolation in the human diet. Whether there is a link between fructose, HFCS, or sucrose and increased risk of heart disease, metabolic syndrome, or fatty infiltration of the liver or muscle remains in dispute with different studies using different methodologies arriving at different conclusions. Further randomized clinical trials are needed to resolve many of these issues. The purpose of this review is to summarize current knowledge about the metabolism, endocrine responses, and potential health effects of sucrose, HFCS, and fructose.

High-fructose corn syrup, energy intake, and appetite regulation

High-fructose corn syrup (HFCS) has been implicated in excess weight gain through mechanisms seen in some acute feeding studies and by virtue of its abundance in the food supply during years of increasing obesity. Compared with pure glucose, fructose is thought to be associated with insufficient secretion of insulin and leptin and suppression of ghrelin. However, when HFCS is compared with sucrose, the more commonly consumed sweetener, such differences are not apparent, and appetite and energy intake do not differ in the short-term. Longer-term studies on connections between HFCS, potential mechanisms, and body weight have not been conducted. The main objective of this review was to examine collective data on associations between consumption of HFCS and energy balance, with particular focus on energy intake and its regulation.

The Effect of High-Fructose Corn Syrup Consumption on Triglycerides and Uric Acid

Rates of overweight and obesity have been on a steady rise for decades, and the problems society faces from this and associated metabolic diseases are many. As a result, the need to understand the contributing factors is great. A very compelling case can be made that excess sugar consumption has played a significant role. In addition, fructose, as a component of the vast majority of caloric sweeteners, is seen to be particularly insidious. Evidence shows that fructose bypasses many of the bodys satiating signals, thus potentially promoting overconsumption of energy, weight gain, and the development on insulin resistance. It has also been shown to increase uric acid levels, which in turn promotes many of the abnormalities seen in the metabolic syndrome including hypertriglyceridemia. However, the main source of fructose in the diet is high-fructose corn syrup (HFCS), an artificially manufactured disaccharide that is only 55% fructose. This review highlights the fact that limited data are available about the metabolic effects of HFCS compared with other caloric sweeteners. The data suggest that HFCS yields similar metabolic responses to other caloric sweeteners such as sucrose.

INTERLEUKIN-15 AND INTERLEUKIN-15Rα SNPs AND ASSOCIATIONS WITH MUSCLE, BONE, AND PREDICTORS OF THE METABOLIC SYNDROME

The aims of this study were to examine associations between two SNPs in the human IL-15 gene and three SNPs in the IL-15Ralpha gene with predictors of metabolic syndrome and phenotypes in muscle, strength, and bone at baseline and in response to resistance training (RT). Subjects were Caucasians who had not performed RT in the previous year and consisted of a strength cohort (n=748), volumetric cohort (n=722), and serum cohort (n=544). Subjects completed 12 weeks of unilateral RT of the non-dominant arm, using their dominant arm as an untrained control. ANCOVA analyses revealed gender-specific associations with: (1) IL-15 SNP (rs1589241) and cholesterol (p=0.04), LDL (p=0.02), the homeostasis model assessment (HOMA; p=0.03), and BMI (p=0.002); (2) IL-15 SNP (rs1057972) and the pre- to post-training absolute difference in 1RM strength (p=0.02), BMI (p=0.008), and fasting glucose (p=0.03); (3) IL-15Ralpha SNP (rs2296135) and baseline total bone volume (p=0.04) and the pre- to post-training absolute difference in isometric strength (p=0.01); and 4) IL-15Ralpha SNP (rs2228059) and serum triglycerides (p=0.04), baseline whole muscle volume (p=0.04), baseline cortical bone volume (p=0.04), and baseline muscle quality (p=0.04). All associations were consistent in showing a potential involvement of the IL-15 pathway with muscle and bone phenotypes and predictors of metabolic syndrome.

Body composition, dietary composition, and components of metabolic syndrome in overweight and obese adults after a 12-week trial on dietary treatments focused on portion control, energy density, or glycemic index

BackgroundGiven the rise in obesity and associated chronic diseases, it is critical to determine optimal weight management approaches that will also improve dietary composition and chronic disease risk factors. Few studies have examined all these weight, diet, and disease risk variables in subjects participating in recommended multi-disciplinary weight loss programs using different dietary strategies.MethodsThis study compared effects of three dietary approaches to weight loss on body composition, dietary composition and risk factors for metabolic syndrome (MetS). In a 12-week trial, sedentary but otherwise healthy overweight and obese adults (19 M & 138 F; 38.7 ± 6.7 y; BMI 31.8 ± 2.2) who were attending weekly group sessions for weight loss followed either portion control, low energy density, or low glycemic index diet plans. At baseline and 12 weeks, measures included anthropometrics, body composition, 3-day food diaries, blood pressure, total lipid profile, HOMA, C-reactive protein, and fasting blood glucose and insulin. Data were analyzed by repeated measures analysis of variance.ResultsAll groups significantly reduced body weight and showed significant improvements in body composition (p < 0.001), and components of metabolic syndrome (p < 0.027 to 0.002), although HDL decreased (p < 0.001). Dietary energy, %fat and %saturated fat decreased while protein intake increased significantly (p < 0.001). There were no significant differences among the three groups in any variable related to body composition, dietary composition, or MetS components.ConclusionDifferent dietary approaches based on portion control, low energy density, or low glycemic index produced similar, significant short-term improvements in body composition, diet compositin, and MetS components in overweight and obese adults undergoing weekly weight loss meetings. This may allow for flexibility in options for dietary counseling based on patient preference.

PPARα L162V underlies variation in serum triglycerides and subcutaneous fat volume in young males

BackgroundOf the five sub-phenotypes defining metabolic syndrome, all are known to have strong genetic components (typically 50–80% of population variation). Studies defining genetic predispositions have typically focused on older populations with metabolic syndrome and/or type 2 diabetes. We hypothesized that the study of younger populations would mitigate many confounding variables, and allow us to better define genetic predisposition loci for metabolic syndrome.MethodsWe studied 610 young adult volunteers (average age 24 yrs) for metabolic syndrome markers, and volumetric MRI of upper arm muscle, bone, and fat pre- and post-unilateral resistance training.ResultsWe found the PPARα L162V polymorphism to be a strong determinant of serum triglyceride levels in young White males, where carriers of the V allele showed 78% increase in triglycerides relative to L homozygotes (LL = 116 ± 11 mg/dL, LV = 208 ± 30 mg/dL; p = 0.004). Men with the V allele showed lower HDL (LL = 42 ± 1 mg/dL, LV = 34 ± 2 mg/dL; p = 0.001), but women did not. Subcutaneous fat volume was higher in males carrying the V allele, however, exercise training increased fat volume of the untrained arm in V carriers, while LL genotypes significantly decreased in fat volume (LL = -1,707 ± 21 mm3, LV = 17,617 ± 58 mm3 ; p = 0.002), indicating a systemic effect of the V allele on adiposity after unilateral training. Our study suggests that the primary effect of PPARα L162V is on serum triglycerides, with downstream effects on adiposity and response to training.ConclusionOur results on association of PPARα and triglycerides in males showed a much larger effect of the V allele than previously reported in older and less healthy populations. Specifically, we showed the V allele to increase triglycerides by 78% (p = 0.004), and this single polymorphism accounted for 3.8% of all variation in serum triglycerides in males (p = 0.0037).

Myostatin and Follistatin Polymorphisms Interact with Muscle Phenotypes and Ethnicity

PURPOSE We examined associations among myostatin (MSTN) 2379 A > G and 163 G > A and follistatin (FST) -5003 A > T and -833 G > T single nucleotide polymorphisms (SNP) on the muscle size and the strength response to resistance training (RT). METHODS Subjects (n = 645, age = 24.1 +/- 0.2 yr, body mass index [BMI] = 24.2 +/- 0.2 kg x m(-2)) self-disclosed themselves as Caucasian (78.9%), African American (3.6%), Asian (8.4%), Hispanic (5.0%), or Other (4.2%). They were genotyped for MSTN 2379 A > G (n = 645), MSTN 163 G > A (n = 639), FST -5003 A > T (n = 580), and FST -833 G > T (n = 603). We assessed dynamic (one repetition maximum [1RM]) and isometric (maximum voluntary contraction [MVC]) muscle strength and size (cross-sectional area [CSA]) of the elbow flexors before and after 12 wk of unilateral upper-arm RT. Repeated-measures ANCOVA tested associations among genetic variants and muscle phenotypes with age and BMI as covariates. RESULTS Baseline MVC was greater among African Americans who were carriers of the MSTN G(2379) allele (AG/GG, n = 15) than the A2379A homozygotes (n = 8; 64.2 +/- 6.8 vs 49.8 +/- 8.7 kg). African Americans who were carriers of the FST T(-5003) allele (n = 12) had greater baseline 1RM (11.9 +/- 0.7 vs 8.8 +/- 0.5 kg) and CSA (24.4 +/- 1.3 vs 19.1 +/- 1.2 cm(2)) than African Americans with the A-5003A genotype (n = 14; P < 0.05). No MSTN or FST genotype and muscle phenotype associations were found among the other ethnic groups (P >or= 0.05). CONCLUSION MSTN 2379 A > G and FST -5003 A > T were associated with baseline muscle strength and size among African Americans only. These ethnic-specific associations are hypothesis generating and should be confirmed in a larger sample of African Americans.

Resistin Polymorphisms Are Associated with Muscle, Bone, and Fat Phenotypes in White Men and Women

Objective: The biological function of resistin (RST) is unknown, although it may have roles in obesity, diabetes, and insulin resistance. The objective of this study was to examine the effects of single nucleotide polymorphisms (SNPs) in the human RST gene on muscle, bone, and adipose tissue phenotypes and in response to resistance training (RT).

The Muscle Strength and Size Response to Upper Arm, Unilateral Resistance Training Among Adults Who Are Overweight and Obese

Overweight and obesity result in musculoskeletal impairments that limit exercise capacity. We examined if the muscle strength and size response to resistance training (RT) differed among 687 young (mean ± SEM, 24.2 ± 0.2 years) overweight and obese (OW) compared to normal weight (NW) adults as denoted by the body mass index (BMI). Subjects were 449 NW (22.0 ± 0.1 kg·m-2, 23.4 ± 0.3 years) and 238 OW (29.2 ± 0.2 kg·m-2, 25.6 ± 0.4 years) men (n = 285) and women (n = 402) who underwent 12 weeks (2 d·wk-1) of RT of the non- dominant arm. Maximum voluntary contraction (MVC) and 1 repetition maximum (1RM) assessed peak elbow flexor strength. Magnetic resonance imaging measured the biceps muscle cross sectional area (CSA). Multiple dependent variable analysis of covariance tested if muscle strength and size differed among BMI groups pre-, post-, and pre-to-post–RT. Overweight and obese had greater MVC, 1RM, and CSA than NW pre- and post- RT (p < 0.001). Maximum voluntary contraction and 1RM gains were not different between BMI groups pre- to post-RT (p ≥ 0.05). When adjusted for baseline values, NW had greater relative MVC (21.2 ± 1.0 vs. 17.4 ± 1.4%) and 1RM (54.3 ± 1.5 vs. 49.0 ± 2.0%) increases than OW (p > 0.05). Normal weight also had greater allometric MVC (0.48 ± 0.02 kg·kg-0.67 vs. 0.40 ± 0.03 kg·kg-0.67) and 1RM (0.25 ± 0.00 vs. 0.22 ± 0.01 kg·kg-0.67) gains than OW (p > 0.05). CSA gains were greater among OW than NW (3.6 ± 0.2 vs. 3.2 ± 0.1 cm2)(p > 0.001); however, relative CSA increases were not different between BMI groups (19.4 ± 0.5 vs. 18.4 ± 0.7%) (p ≥ 0.05). Despite similar relative muscle size increases, relative and allometic strength gains were less among OW than NW. These findings indicate the short-term relative and allometric muscle strength response to RT may be attenuated among adults who are overweight and obese.

Lack of evidence for high fructose corn syrup as the cause of the obesity epidemic

High fructose corn syrup (HFCS) is one of the most misunderstood food ingredients. HFCS was developed in the mid-1960s as an alternative to sucrose and because of its physical and functional properties, was widely embraced by the food industry. The use of HFCS grew rapidly from 1970–1999, principally as a replacement for sucrose. HFCS usage in the United States peaked in 1999 and it has been in decline since that time. At its peak, HFCS was still less consumed in the United States than was sucrose, although sucrose did have a significant decline in usage during the time that HFCS usage increased. Worldwide, sucrose is still the dominant sweetener with over nine times as much consumption as HFCS.