Progress 10/01/01 to 09/30/05
Outputs
In the course of our studies we have been able to make significant contributions regarding the metabolic impact of dietary supplements including choline and carnitine with or without caffeine and life style change (exercise). Choline and carnitine are richly supplied in our normal omnivorous diet and their deficiency is uncommon among our people. However, when these nutrients are given in a combination as a supplement there is perturbation of metabolic process as we have been able to demonstrate in animals and humans. The metabolic consequences include preferential conservation of carnitine in all tissues especially in the skeletal muscle, loss of body fat, accretion of proteins, incomplete oxidation of fatty acids and their excretion in urine as short-chain acylcarnitines, reduction in fatty acid synthesis and species-specific reduction in oxidative stress. These results indicate that the combination of nutrients have different effects than a single nutrient in an
intact animal/human where the perturbation affects more than one system in a manner that is not easily explained by our current understanding the metabolic processes.
Impacts
Since a variety of supplements are commonly used, it is important to realize that multi-nutrient supplementation has multifaceted impact on our systems for which careful monitoring is essential to avoid health risks. Through our research we can identify risks and benefits of nutritional supplements, which are becoming widely used among a large segment of our society. The result will be a more knowledgeable public, better able to control nutritional disorders and choose healthier foods, which in turn should lead to a greater health and well-being of a large segment of our society.
Publications
- Sachan, D.S., Hongu, N. & Johnsen, M. 2005. Decreasing oxidative stress with choline and carnitine in women. J. Am. Coll. Nutr. 24: 172-176.
- Grant, L. P., Haughton, B. & Sachan, D.S. 2004. Nutrition education is positively associated with substance abuse treatment program outcomes. J. Am. Diet. Assoc.104: 604 - 610.
- Sachan, Dileep S. and Hongu, N. 2004. Ketogenic effect of supplementary choline and carnitine in normal humans and animals. J. Am. Coll. Nutr. 23: A463.
- Sachan, Dileep S. and Hongu, N. 2004. Dietary carnitine, choline and caffeine supplementation decreases insulin and activities of lipogenic enzymes as does exercise. FASEB J. 18: A875.
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Progress 01/01/04 to 12/31/04
Outputs
We have previously reported significant decrease in body fat and serum leptin in rats fed diet supplemented with a combination of carnitine, choline and caffeine(CCC) and provided support for enhanced fatty acid oxidation (J Nutr 2000, J Nutr Biochem 2000). We have since documented increased formation of ketones in animals given various combination of CCC which supports fatty acid mobilization, oxidation and disposal of fat in urine. In addition, we have studied changes in serum insulin and activities of lipogenic enzymes in the CCC rats. Twenty male SD rats were placed into 4 groups with and without (N) supplement (S) or exercise (E): NSNE; NSE; SNE and SE. Exercise trained rats ran for 6 d/wk, 25 min/d at 18m/m for 3wk. A day after the last bout of exercise, epididymal fat and serum were collected and frozen at -80 degree C. The activities of fatty acid synthase (FAS), glycerol-3-phosphatedehydrogenase (G3PDH), and glucose-6-phosphatedehydrogenase (G6PDH) were
determined in the epididymal fat. Compared to the NSNE group, the NSE, SNE, and SE groups had significantly lower insulin concentration, 10.1, 7.8, 6.9, and 6.0 ng/mL, respectively (p<0.05). The activities of FAS, G3PDH and G6PDH in the epididymal fats of the NSE, SNE and SE rats were significantly lower than those of NSNE rats. Reduction in the activities of lipogenic enzymes of S and E groups was in concert with the changes in the epididymal fat of these groups. It is concluded that dietary CCC supplementation with or without exercise attenuates fatty acid synthesis, which is magnified with exercise. Thus the combination of enhanced oxidation and reduced biosynthesis of fatty acids induced by CCC contributes to the previously reported leaner composition of body mass.
Impacts
A combination of choline and carnitine supplementation of usual American diet results in increased fat metabolism and protects against oxidative stress. This knowledge may have positive impact on sale of commodities like milk, meat, beans and grains; and may also provide justification for marketing of dietary supplements.
Publications
- No publications reported this period
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Progress 01/01/03 to 12/31/03
Outputs
We have shown in earlier reports that diet supplemented with choline, carnitine and caffeine in animal models and choline and carnitine in humans enhance fat catabolism and thus reduces body fat. Because choline supplementation caused apparent carnitine deficiency in humans we investigated if carnitine loading prior to choline supplementation will prevent this deficiency. The results indicted that carnitine preloading for 7days buffers choline-induced carnitine deficit when carnitine continues to be supplemented with choline. However, if carnitine is supplemented after initiating the subjects on choline first, carnitine deficit persists for a longer duration. Since choline and carnitine enhanced fatty acid oxidation, a mitochondrial event, we investigated if this may result in increased oxidative stress in the choline and carnitine supplemented men and women. Serum TBARS, a marker of total lipid peroxidation, was significantly lower in the people with supplements and
this effect was not adversely affected by the mild exercise regimen (walking). Serum retinol and tocopherol concentrations were supportive of the reduced oxidative stress. These results allow the conclusion that dietary supplementation with choline and carnitine protects against lipid peroxidation in spite of increasing fatty acid catabolism in humans.
Impacts
A combination of choline and carnitine supplementation of usual American diet results in increased fat metabolism and protects against oxidative stress. This knowledge may have positive impact on sale of commodities like milk, meat, beans and grains; and may also provide justification for marketing of dietary supplements.
Publications
- Hongu, N. and Sachan, D.S. 2003. Carnitine and choline supplementation with exercise alters carnitine profiles, biochemical markers of fat metabolism and serum leptin concentration in healthy women. J. Nutr. 133: 84-89.
- Hongu, Nobuko, Johnsen, Maike and Sachan, Dileep S. 2003. Choline and carnitine supplements decrease oxidative stress in humans. J. Am. Coll. Nutr. 22: 470. (Abstr.)
- Sachan, Dileep S. and Hongu, Nobuko .2003. Carnitine preloading averts choline-induced carnitine deficit in humans. FASEB J. 17: A734. (Abstr.)
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Progress 01/01/02 to 12/31/02
Outputs
In previous reports we have shown that choline, carnitine and/ or caffeine enhanced fat metabolism in animal models i.e. rats and guinea pigs. Now we report the results of a study completed in humans. The objective was to determine effects of supplementary choline, carnitine and combination of the two with or without exercise on serum and urinary carnitine profiles and biochemical markers of fatty acid oxidation in healthy humans. Nineteen women divided in 3 groups were given placebo or choline or carnitine for 1 wk; and placebo or choline plus carnitine for additional wk. While there was no change in the placebo group, serum and urinary carnitine were decreased in the choline supplemented group. Introduction of carnitine to the choline group restored serum and urinary carnitine profiles. Serum and urinary carnitine increased in carnitine supplemented group and introduction of choline to the carnitine group depressed serum and urinary carnitine, but it remained well
above normal. The concentrations of serum beta-hydroxybutyrate and serum as well as urinary acetylcarnitine were elevated by the supplements. A mild exercise regimen increased concentration of serum beta-hydroxybutyrate, serum as well as urinary acetylcarnitines; and decreased serum leptin concentrations in all groups. The effects of supplements are sustained until 2 wk following cessation of supplementation and exercise. It is concluded that choline-induced decrease in serum and urinary carnitine is buffered by carnitine preloading, and these supplements shift tissue partitioning of the nutrients so as to favor fat mobilization, partial oxidation of fatty acids and disposal of energy substrate carbons in urine of humans. Thus in humans choline and carnitine rich foods such as milk, meat and soy may help fat loss.
Impacts
The judicious combination of nutrients as dietary supplements, selected on the basis of their biochemical functions, hold promise for healthy weight and body composition. Most all these nutrients are present in our daily diet of milk, meat,beans and cereals.
Publications
- Sachan, D.S., Yatim, A.M. and Daily, J.W. 2002. Comparative effects of dietary corn oil, Safflower oil, fish oil and palm oil on metabolism of ethanol and carnitine in the rat. J. Am. Coll. Nutr . 21: 233-238.
- Hongu, N. and Sachan, D.S. 2002. Tissue carnitine accretion and fat metabolism in rats supplemented with carnitine, choline and caffeine regardless of exercise. J. Medical Sciences 2: 59-64.
- Hongu, Nobuko and Sachan, Dileep S. 2002. Carnitine preloading and mild exercise ameliorate serum lipid and leptin concentrations in humans. J. Am. Coll. Sports Med. 34: S86.
- Sachan, Dileep S. and Hongu, Nobuko. 2002. Promotion of fatty acid catabolism by choline and carnitine supplementation in humans. FASEB J. 16: A988.
- Grant, Louise P., Haughton, Betsy and Sachan, Dileep S. 2002. Survey of Nutrition Intervention in VA Substance Abuse Treatment Programs. FASEB J. 16: A1021.
- Hongu, Nobuko and Sachan, Dileep S. 2002. Reduction in serum leptin concentration after one week of mild exercise regimen in untrained men and women. FASEB J. 16: A628.
- Daily, J.W., Park, E.S., Hongu, N. and Sachan, D.S. 2002. Choline-induced carnitine conservation by increased fractional tubular reabsorption of carnitine in guinea pigs. Nutr. Res. 1219-1230.
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