Iron Fortification and Supplementation: Fighting Anemia of Chronic Diseases or Fueling Obesity?

The significant worldwide increase in obesity has become a major health problem. Excess adiposity has been extensively linked to inflammation. Recently, studies have shown that dietary intake and microbiota dysbiosis can affect the health of the gut and lead to low-grade systemic inflammation, worsening the state of obesity and further exacerbating inflammation. The latter is shown to decrease iron status and potentially increase the risk of anemia by inhibiting iron absorption. Hence, anemia of obesity is independent of iron intake and does not properly respond to increased iron ingestion. Therefore, countries with a high rate of obesity should assess the health impact of fortification and supplementation with iron due to their potential drawbacks. This review tries to elucidate the relation between inflammation and iron status to better understand the etiology of anemia of obesity and chronic diseases and wisely design any dietary or medical interventions for the management of anemia and/or obesity.

Phosphorus Supplementation Mitigated Food Intake and Growth of Rats Fed a Low-Protein Diet.

Background: Low protein intake is associated with various negative health outcomes at any life stage. When diets do not contain sufficient protein, phosphorus availability is compromised because proteins are the major sources of phosphorus. However, whether mineral phosphorus supplementation mitigates this problem is unknown, to our knowledge. Objective: Our goal was to determine the impact of dietary phosphorus supplementation on food intake, weight gain, energy efficiency, body composition, blood metabolites, and liver histology in rats fed a low-protein diet for 9 wk. Methods: Forty-nine 6-wk-old male Sprague-Dawley rats were randomly allocated to 5 groups and consumed 5 isocaloric diets ad libitum that varied only in protein (egg white) and phosphorus concentrations for 9 wk. The control group received a 20% protein diet with 0.3% P (NP-0.3P). The 4 other groups were fed a low-protein (10%) diet with a phosphorus concentration of 0.015%, 0.056%, 0.1%, or 0.3% (LP-0.3P). The rats' weight, body and liver composition, and plasma biomarkers were then assessed. Results: The addition of phosphorus to the low-protein diet significantly increased food intake, weight gain, and energy efficiency, which were similar among the groups that received 0.3% P (LP-0.3P and NP-0.3P) regardless of dietary protein content. In addition, phosphorus supplementation of low-protein diets reduced plasma urea nitrogen and increased total body protein content (defatted). Changes in food intake and efficiency, body weight and composition, and plasma urea concentration were highly pronounced at a dietary phosphorus content <0.1%, which may represent a critical threshold. Conclusions: The addition of phosphorus to low-protein diets improved growth measures in rats, mainly as a result of enhanced energy efficiency. A dietary phosphorus concentration of 0.3% mitigated detrimental effects of low-protein diets on growth parameters.

Phosphorus Supplementation Recovers the Blunted Diet-Induced Thermogenesis of Overweight and Obese Adults: A Pilot Study.

Diet-induced thermogenesis (DIT) is believed to be largely related to ATP production, which is dependent on phosphorus (P) availability. We aimed to test the effect of P addition on DIT of lean and overweight/obese healthy subjects. DIT was measured with or without P in 10 lean and 13 overweight/obese adults in a double-blind randomized cross-over pilot study with one week washout period. After 10 h overnight fast, resting metabolic rate, respiratory quotient, and substrate utilization were measured at fasting and every 30 min for 3 h after subjects drank a standardized glucose solution, with P (500 mg) or placebo pills. Subjective ratings of hunger and satiety were assessed before and after the end of each experiment using validated visual analogue scale (VAS) questionnaires. Overweight/obese subjects had a blunted DIT with placebo, while P supplementation induced a 23% increase in their DIT area under the curve (p < 0.05), which was associated with a significant increase in carbohydrate oxidation. Subjects had lower appetite following P supplementation, which was expressed as a significantly (p = 0.02) lower desire to eat a meal (4.0 ± 0.7 cm) compared with placebo (5.8 ± 0.9 cm). P supplementation recovers the blunted diet-induced thermogenesis in overweight and obese subjects and enhances their postprandial satiety.

Combined fish oil and high oleic sunflower oil supplements neutralize their individual effects on the lipid profile of healthy men.

Both n-3 and n-9 fatty acids share a common metabolic pathway and can potentially and individually improve cardiovascular disease risk factors. Dietary n-6 is known to weaken the efficacy of n-3 fatty acids due to competition for the same enzymes. Still unclear is whether a similar competition exists between n-3 and n-9 fatty acids. Thus, a 12-week intervention study was conducted to investigate the effect of different combinations of fish oil and high-oleic sunflower oil (OSO) on healthy subjects. Included were five groups (98 subjects): three groups received a fixed amount of n-9 (8 g/day) with varying amounts of n-3 (1, 2 or 4 g/day), one group was given n-3 fatty acids only (2 g/day) and another was given n-9 only (8 g/day). We found that fish oil supplement (2 g/day) was able to decrease TAG by about 13 %, this effect was diminished with the co-ingestion of n-9 (OSO). Intake of OSO (8 g/day) reduced both total and LDL cholesterol by about 10 %, this effect was reduced by the addition of fish oil. Both fish oil and OSO failed to have any significant effect on both glycemic and blood pressure parameters. In conclusion; the impact of oleic acid (n-9) on total and LDL cholesterol was altered by the addition fish oil (n-3). These effects may have been the result of enzymatic competition between the two types of fatty acids.

Effect of lysine, vitamin B(6), and carnitine supplementation on the lipid profile of male patients with hypertriglyceridemia: a 12-week, open-label, randomized, placebo-controlled trial.

BACKGROUND: Fat metabolism is known to be altered in hypertriglyceridemia. Fat oxidation requires carnitine, which can be obtained either from the diet (animal or dairy products) or through synthesis in the body using both lysine and vitamin B(6). OBJECTIVE: The goal of this study was to investigate the effect of lysine, vitamin B(6), and carnitine supplementation on both glycemia and the lipid profiles, specifically triglyceride (TG) levels, in men with hypertriglyceridemia. METHODS: This 12-week, randomized, placebo-controlled clinical trial was conducted at a Lebanese medical center. A total of 85 hypertriglyceridemic (TG> 150 mg/dL) male patients were randomized to 1 of 5 groups and given supplements of lysine (1 g/d), vitamin B(6) (50 mg/d), lysine (1 g/d) + vitamin B(6) (50 mg/d), carnitine (1 g/d), or placebo for 12 weeks. The lipid profile (TG, total cholesterol, LDL-C, and HDL-C) and fasting plasma glucose levels were assessed at baseline and at 6 and 12 weeks. RESULTS: Adults (∼50 years) Lebanese males from a low socioeconomic status in Beirut were given the appropriate supplements. Vitamin B(6) supplementation was associated with a significant reduction in total cholesterol and HDL-C of ∼10%. In addition, plasma TG was reduced by 36.6 mg/dL at 6 weeks, whereas levels in the placebo group increased by 18 mg/dL; this difference failed to reach statistical significance. No major changes in the lipid profile were observed in the lysine and carnitine groups or when lysine was added to vitamin B(6). CONCLUSION: Vitamin B(6) supplementation in these male patients with hypertriglyceridemia reduced plasma total cholesterol and HDL-C concentrations.

Stimulation of postprandial in vivo glycogenesis and lipogenesis of rats fed high fructose diet with varied phosphate content.

It has been reported that increased fructose intake is associated with the development of the metabolic syndrome. The phosphate (P) sequestering capacity of fructose is likely to affect the phosphorylation capacity of different metabolites, and this, in turn, may be the basis for several metabolic derangements, especially in the P requiring reactions, for example, glycogenesis and lipogenesis. We hypothesized that P enrichment of the diet can balance P status and, consequently, affect glycogenesis and lipogenesis. An animal experiment was executed in which adult male Sprague-Dawley rats were maintained for 4 days on high-fructose diets with different P content (0.15%, 0.165%, 0.30%, and 1.65%). At the end of the feeding period, overnight fasted rats were tube fed a test meal, injected with (3)H(2)O and euthanized 1 hour later. Final plasma glucose, insulin, uric acid, and triacylglycerol concentrations, as well as in vivo rates of glycogen and lipid synthesis and hepatic glycogen content, were measured. Results showed that increased P content of the diet was associated with an increase in postprandial epididymal fat pad (P = .007) and hepatic lipogenesis (P = .029), as well as glycogenesis (P = .024). In conclusion, P content of the diet was found to stimulate both glycogenesis and lipogenesis. These alterations in carbohydrate and fat metabolism point to the potential of P in influencing nutritional status.

Meal pattern of male rats maintained on histidine-, leucine-, or tyrosine-supplemented diet.

OBJECTIVE: Food intake is known to be affected by macronutrient composition of the diet, and protein manipulation has been reported to alter food intake, but the effect of individual amino acids on eating behavior has not been fully studied. This study investigated the effect of diet supplementation with three individual amino acids on meal pattern in male rats. RESEARCH METHODS AND PROCEDURES: Thirty-two Sprague-Dawley rats were randomly divided into four equal groups and fed control diet or histidine (5%)-, leucine (5%)-, or tyrosine (5%)-supplemented diet for 2 weeks and were monitored for their meal pattern. RESULTS: Total food intake and feeding rate of the different groups were not affected, although other components of meal pattern were altered. Histidine supplementation reduced diurnal meal size by 42% (p < 0.05), whereas that of leucine increased nocturnal meal size by approximately 35% (p < 0.05). Tyrosine supplementation increased food intake of the nocturnal period and decreased that of the diurnal period. Both histidine and tyrosine supplementation elevated fasting plasma insulin levels and suppressed fasting glucose significantly. DISCUSSION: Individual amino acids were found to alter meal pattern differently. Further investigations are required to dissect the involvement of central and peripheral factors in these alterations.

The effect of glutamine and dihydroxyacetone supplementation on food intake, weight gain, and postprandial glycogen synthesis in female Zucker rats.

OBJECTIVE: We sought to test the hypothesis that increasing postprandial hepatic glycogen synthesis rate would decrease food intake and growth rate in obese Zucker rats. DESIGN: Supplements of glutamine, with and without dihydroxyacetone (DHA), which have previously been shown to stimulate hepatic glycogen synthesis, were administered in the diet of obese Zucker rats for periods of 1 and 3 wk. MEASUREMENTS: Food intake and body weight were monitored throughout the experiments. At the end of the feeding period the rats were fed a test meal and injected with (3)H(2)O to measure in vivo rates of glycogen and lipid synthesis. Final plasma glucose and triacylglycerol and hepatic glycogen content were also determined. Carcass fat and water contents were also measured in the 3-wk study. RESULTS: Dietary glutamine had no effect on food intake, weight gain, or body composition. Addition of DHA caused a reduction in food intake and weight gain and a stimulation of in vivo hepatic glycogen synthesis after 1 wk, but these changes were abolished by the end of 3 wk. Hepatic lipogenesis in vivo was increased by DHA treatment for 1 and 3 wk. CONCLUSIONS: Stimulation of hepatic glycogen synthesis by DHA treatment was associated with a reduction in food intake. However, the effect of DHA on glycogen synthesis and food intake disappeared after 3 wk of supplementation.

Effect of diet supplementation with glutamine, dihydroxyacetone, and leucine on food intake, weight gain, and postprandial glycogen metabolism of rats.

OBJECTIVE: We tested the hypothesis that increasing the rate of postprandial hepatic glycogen synthesis would decrease food intake and growth rate in normal rats. METHODS: Diets supplemented with glutamine, glutamine plus dihydroxyacetone, and glutamine plus dihydroxyacetone plus leucine were administered to male Sprague-Dawley rats for 1 wk. These are combinations that have been shown to stimulate hepatic glycogen synthesis in vitro. Food intake and body weight were monitored throughout the experiment. At the end of the feeding period, rats were fed a test meal and injected with 3H2O to measure in vivo rates of glycogen and lipid synthesis. Positional analysis of the 3H incorporated into glycogen was used to determine the proportion of glycogen synthesized via pyruvate. Final levels of plasma glucose and triacylglycerol and hepatic glycogen were also measured. RESULTS: Dietary glutamine increased hepatic glycogen synthesis. Addition of dihydroxyacetone, with or without additional leucine, caused an additional increase in hepatic glycogen synthesis and increased the proportion of glycogen synthesized via pyruvate. Lipogenesis was not altered in the liver or adipose tissue. None of the dietary treatments had any effect on food intake, but the diets that contained dihydroxyacetone decreased the rate of weight gain. CONCLUSIONS: Increasing glycogen synthesis had no effect on food intake. Increasing the proportion of glycogen synthesized by the indirect pathway through pyruvate was associated with a decrease in weight gain.