Some of the Science Behind the Supplement Formulations Supplements We Take with Our Meals to Enhance Health and Healthy Weight Management By Durk Pearson & Sandy Shaw e recommend—and take ourselves—several supplements for healthy weight management: 3-acetyl-7-oxo-DHEA, chromium polynicotinate, resveratrol, grape seed extract, and purple corn color (anthocyanins). These help Sandy to maintain her weight at its longtime level (she’s 5’3” and weighs 112 pounds) and Durk to sustain the 35 pounds he lost by the techniques we described earlier, and to get rid of more fat. (Durk’s weight gain came about largely due to unfortunate genetic heritage; his father, who died in his early 70s, had an enormous paunch.) These supplements help to maintain healthy postprandial (after-meal) glucose and fat levels by controlling absorption of fat and glucose, reducing postprandial fat and glucose synthesis pathways, and increasing energy expenditure. It is the increased levels of fat and glucose in the bloodstream following eating that cause most of their unhealthful effects as compared to their fasting levels, so for best health, our goal is to decrease excessive appearance of fat and glucose in the blood following meals. It is noteworthy that in life extension studies in mammals, caloric restriction reduces glucose and insulin levels; hence, reducing glucose and insulin mimics at least these aspects of caloric restriction. In one caloric restriction study that we have discussed earlier (Zangarelli et al., 2006),* restriction of only carbohydrate calories in rats (without restricting protein and fat calories as compared to ad libitum-fed rats) resulted in similar effects to those seen in the all-calorie-restricted rats in the study, except that the rats with only carbohydrate calories restricted were stronger and had better muscle function in late middle age. *See the section “Additional Benefits of Caloric Restriction When Only Carbohydrate Calories Are Restricted” in the December 2006 issue of our Life Extension News, published in Life Enhancement, February 2007. Other effects (described in detail below) included: Reduction of or prevention of fat accumulation in animals on a high-fat diet Improved insulin sensitivity Improved mitochondrial function Increased muscle strength Increased HDL-cholesterol Decreased LDL-cholesterol Antiatherosclerotic Anti-inflammatory Reference Zangarelli et al. Synergistic effects of caloric restriction with maintained protein intake on skeletal muscle performance in 21 month old rats: a mitochondria-mediated pathway. FASEB J 20:2439-50 (2006). 3-Acetyl-7-Oxo-DHEA As Durk lost fat, his metabolism counteracted his fat-loss program by reducing his basal metabolism. Durk developed cold hands, feet, and nose as his body tried to conserve energy. This is a normal and expected phenomenon during weight loss, which makes further loss more and more difficult. What to do? Fortunately, there is a solution: a DHEA metabolite, 7-oxo-DHEA, or its acetylated form, 3-acetyl-7-oxo-DHEA. There are many DHEA metabolites whose functions are relatively uninvestigated and unknown, perhaps owing to the difficulties in obtaining enforceable patents on natural substances, which are discoveries (hence unpatentable) rather than inventions. 7-Oxo-DHEA is a DHEA metabolite that cannot be converted to either testosterone or estradiol, or to other androgens or estrogens. By the age of 40, humans produce only about 40% of the 7-oxo-DHEA that they produced as young adults, and this decline continues with age. 7-Oxo-DHEA is not an inert substance, however. It increases the levels of two enzymes that are involved in thermogenesis, enzymes that are also increased by thyroid hormone. These enzymes are glycerol-3-phosphate dehydrogenase and cytosolic malic enzyme. DHEA itself had no statistically significant effect on these two enzymes when fed to rats at 0.01% of their diet, but 7-oxo-DHEA fed at 0.01% caused an increase of 183% in glycerol-3-phosphate dehydrogenase, and a 299% increase in cytosolic malic enzyme. (Lardy, 1995) Natural substances are often acetylated to increase their bioavailability (and patentability). A double-blind placebo-controlled human trial has been performed using 3-acetyl-7-oxo-DHEA to determine its usefulness for weight loss at a dose of 100 mg twice per day. Middle-aged men and women were encouraged to consume an 1800-calorie/day diet and perform 3 hours per week of supervised exercise. Over an 8-week period, those receiving the 3-acetyl-7-oxo-DHEA lost statistically significantly more weight than the placebo group (–2.88 kg vs. –0.97 kg; P=0.01) and statistically significantly more body fat (–1.8% vs. –0.57%; P=0.02). Most interestingly, the levels of the active form of thyroid hormone, T3, increased by 17.88 ng/dl in the supplemented group, compared to only 2.75 ng/dl in the placebo group (this difference was significant at the P=0.04 level). T3 is the thermogenically active form of thyroid hormone. The thyroid gland makes T4 when stimulated by TSH from the pituitary gland, and some of the T4 is converted to T3. There were no statistically significant changes in either T4 or TSH, which suggests that conversion of T4 to T3 may have been enhanced. (Kalman, 2000) Did it work for Durk? Taking 100 mg of 3-acetyl-7-oxo-DHEA twice per day promptly eliminated his cold hands, feet, and nose. When he stopped taking it, they quickly returned. This experiment was repeated several times. Although it was not double-blind placebo-controlled, Durk is a poor placebo responder, and placebo responses rarely last for the several months that Durk has been using this supplement. References Kalman, Colker, et al. A randomized double-blind placebo-controlled study of 3-acetyl-7-oxo-dehydroepiandrosterone in healthy overweight adults. Curr Ther Res 61(7):435-42 (2000). Lardy, Partridge, et al. Ergosteroids: induction of thermogenic enzymes in liver of rats treated with steroids derived from dehydroepiandrosterone. Proc Natl Acad Sci USA 92:6617-9 (1995). Niacin-Bound Chromium (Chromium Polynicotinate) Chromium has long been known to be essential for glucose and lipid metabolism. Studies have reported lower levels of chromium in the blood of diabetic as compared to normal humans (Jain, 2001). Animal and human diabetic studies have reported lower glucose and triglyceride levels with chromium supplementation (Jain, 2001). Other papers have described chromium-induced improvements in insulin sensitivity (Kegley, 1997) and decreases in systolic blood pressure resulting from elevated sucrose intake (Preuss, 1998). A combination of niacin and chromium has been reported to significantly decrease total cholesterol and total lipid levels in serum (paper cited in Rink, 2006). A particularly interesting recent study (Rink, 2006) reported the results of a mouse genome expression array on subcutaneous fat in type 2 Leprdb obese diabetic mice that were supplemented with niacin-bound chromium. These mice are an extreme model of diabetes and obesity. The animals homozygous (two defective copies) for the diabetes spontaneous mutation (Leprdb) become identifiably obese around 3–4 weeks of age. Elevations of plasma insulin begin at 10–14 days, and of blood glucose at 4–8 weeks. These mice eat and drink excessively and urinate at high levels (as do untreated human diabetics). Insulin treatment fails to control their blood sugar levels, and gluconeogenesis (glucose production) in the liver increases. There is an uncontrolled rise in blood sugar, severe depletion of the insulin-producing beta cells of the pancreatic islets, and death by 10 months of age. The authors chose these severely impaired animals—a powerful model of the metabolic syndrome—to study the effects on gene expression of supplementation with niacin-bound chromium. There were no overt differences in body weight between those mice supplemented with niacin-bound chromium and those receiving placebo. However, the mice supplemented with niacin-bound chromium had significantly (20%) lower total cholesterol, higher (25%) HDL-cholesterol, lower (54%) LDL-cholesterol, and lower (43%) triglyceride levels compared with placebo mice after 6 weeks. The authors cite a paper that reported that, following 6 months of niacin-bound chromium supplementation, significant improvements were found in LDL-cholesterol, total-to-HDL-cholesterol ratios, and total cholesterol levels. With niacin-bound chromium, mice had lower total cholesterol (–20%), higher HDL (+25%), lower LDL (–54%), and lower triglyceride (–43%) levels. The authors report that a large number of the genes upregulated by 1.6-fold or greater in adipose cells were myogenic (genes found in muscle tissue). Indeed, they report that it has recently been shown that preadipocytes (the precursors of adipocytes) are capable of myogenic differentiation. “Genes encoding proteins involved in glycolysis, muscle contraction, muscle metabolism, and muscle development were specifically upregulated in response to NBC [niacin-bound chromium] supplementation. Expression of muscle-specific genes in the fat tissue is known, over time, to diminish the fat content of the tissue.” Resveratrol-treated mice gained less weight, especially on a high-fat diet; compared to nontreated high-fat-fed mice, they had increased muscle strength. Another paper reviewed the toxicity and oxidative mechanisms of different forms of chromium (Bagchi, 2002). The authors summarize: “Comparative studies of chromium (III) picolinate and niacin-bound chromium (III), two popular dietary supplements, reveal that chromium (III) picolinate produces significantly more oxidative stress and DNA damage. Studies have implicated the toxicity of chromium picolinate in renal impairment, skin blisters and pustules, anemia, hemolysis, tissue edema, liver dysfunction, neuronal cell injury, impaired cognitive, perceptual and motor activity, enhanced production of hydroxyl radicals, chromosomal aberrations, depletion of antioxidant enzymes, and DNA damage. Recently, chromium picolinate has been shown to be mutagenic, and picolinic acid moiety appears to be responsible, as studies show that picolinic acid alone is clastogenic [induces DNA damage that can be seen in a microscope]. Niacin-bound chromium (III) has been demonstrated to be more bioavailable and efficacious, and no toxicity has been reported.” References Bagchi, Stohs, et al. Cytotoxicity and oxidative mechanisms of different forms of chromium. Toxicology 180:5-22 (2002). This study was supported in part by grants from the Air Force Office of Scientific Research (#94-1-0048 and #97-1-0016). It should be noted that two of the five scientists involved in the study worked at the InterHealth Research Center. InterHealth Corp. owns the patent on niacin-bound chromium. We are familiar with the work of Dr. Harry G. Preuss, in whose laboratory the work was done and who is listed last, and he is a highly reputable scientist. Jain and Kannan. Chromium chloride inhibits oxidative stress and TNF-alpha secretion caused by exposure to high-glucose in cultured U937 monocytes. Biochem Biophys Res Commun 289:687-91 (2001). Kegley, Spears, Eisemann. Performance and glucose metabolism in calves fed a chromium-nicotinic acid complex or chromium chloride. J Dairy Sci 80:1744-50 (1997). Preuss, Jarrell, et al. Comparative effects of chromium, vanadium and Gymnema sylvestre on sugar-induced blood pressure elevations in SHR. J Am Coll Nutr 17(2):116-23 (1998). Rink, Roy, et al. Transcriptome of the subcutaneous adipose tissue in response to oral supplementation of type 2 Leprdb obese diabetic mice with niacin-bound chromium. Physiol Genomics 27:370-9 (2006). This work was supported in part by National Institute of Health grants GM-069589 and HL-073087. Dr. Bagchi, one of the authors of this study, is Professor, Dept. of Pharmacy Sciences, Creighton University Medical Center, Omaha, NE, and also Senior Vice President, Research & Development, InterHealth Nutraceuticals, Benicia, CA 94510. We are very happy to see dietary supplement ingredient companies hire capable scientists and invest substantial amounts of money in research. Resveratrol You can hardly be unaware of the excitement about resveratrol, a substance (3,4’,5-trihydroxy-trans-stilbene) found in grape skins, peanuts, red wine, cranberry juice, and in smaller amounts in some other fruits—even very small amounts in tomatoes. The plants make it for its antifungal, antimicrobial, and antioxidant properties. Resveratrol has been found to have anti-inflammatory, neuroprotective, antiviral, and cardioprotective effects (reviewed in Krishna et al., 2001), as well as anticancer properties (Alkhalaf and Jaffal, 2006; Cardile et al., 2003; Mousa et al., 2005) and life-extending effects in invertebrates (fruit flies and C. elegans), as well as in a short-lived fish (Wood et al., 2004; Valenzano et al., 2006). Resveratrol improves mitochondrial function and increases energy expenditure Lifespan extension by resveratrol involves the activation of the SIRT1 gene and increased activity of the coactivator PGC-1alpha (PPARgamma coactivator-1alpha) (Lagouge et al., 2006). We have written about the improved mitochondrial function resulting from increased PGC-1alpha activity in our Life Enhancement article about our new ShapeShifter Teas™ (see “Cocktail of Selected Teas for Better Health and Weight Loss” in the April 2007 issue). As we wrote there, PGC-1alpha activity is increased by inhibitors of fatty acid synthase, the final enzyme in the fat-synthesis pathway. By inhibiting fatty acid synthase, malonyl-CoA, the substrate of fatty acid synthase, piles up because it is not being used to synthesize fat (or at least the fat-synthesis rate is significantly inhibited). This has been shown to result in an increase in the activity of PGC-1alpha, an important cellular coactivator that is responsible for mitochondrial biogenesis (creation of new mitochondria), increased energy expenditure, and thermogenesis. Now resveratrol has also been shown to increase the activity of PGC-1alpha. PGC-1alpha is an important molecule for the maintenance of mitochondrial function (which decreases with normal aging) and for increasing energy expenditure, thus helping to avoid weight gain. "Exercise in a pill"? © iStockphoto.com/Liv Friis-Larsen Resveratrol protected mice against diet-induced obesity and insulin resistance, and it increased muscle strength Moreover, the study by Lagouge et al. (2006) showed that resveratrol caused mice to be resistant to diet-induced obesity (resulting from a high-fat diet) and insulin resistance. The animals were given 200–400 mg/kg • day of resveratrol orally in their diet, either regular chow or a high-fat diet, for 15 weeks. Under chow-fed conditions, the authors report that the resveratrol-treated mice tended to gain less weight as compared to controls; this effect became significant when the animals were given a high-fat diet. In fact, the resveratrol-treated high-fat-fed mice weighed almost the same as the chow-fed mice. Moreover, as compared to the nontreated high-fat-fed mice, the resveratrol-treated high-fat-fed mice had increased muscle strength. Interviews in the New York Times and the Washington Post were said to have quoted the paper’s lead author: “Resveratrol makes you look like a trained athlete without the training” and “their [the mice’s] muscle fibers had been remodeled by the drug [resveratrol] into the type more prevalent in trained human athletes.” Could we be approaching “exercise in a pill”? References Alkhalaf and Jaffal. Potent antiproliferative effects of resveratrol on human osteosarcoma SJSA1 cells: novel cellular mechanisms involving the ERKs/p53 cascade. Free Rad Biol Med 41:318-25 (2006). Cardile et al. Involvement of HSP70 in resveratrol-induced apoptosis of human prostate cancer. Anticancer Res 23:4921-6 (2003). Krishna et al. Biological effects of resveratrol. Antiox Redox Signaling 3:1041-64 (2001). Lagouge et al. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell 127(6): 1109-22 (2006). Mousa et al. Effect of resveratrol on angiogenesis and platelet/fibrin-accelerated tumor growth in the chick chorioallantoic membrane model. Nutr Cancer 52(1):59-65 (2005). Valenzano et al. Resveratrol prolongs lifespan and retards the onset of age- related markers in a short-lived vertebrate. Curr Biol 16:296-300 (2006). Wood et al. Sirtuin activators mimic caloric restriction and delay ageing in metazoans. Nature 430(7000):686-9 (2004). Grape Seed Extract Grape seed extract is rich in proanthocyanidins, a class of flavonoids that are comprised of oligomeric (several molecules linked together) catechins, as are found in red wine, grapes, cocoa, apples, and teas (Camellia sinensis), and in especially large amounts in green tea. Proanthocyanidins have been reported to have several healthful effects, including antihyperglycemic, insulin sensitivity-improving, antioxidant, cardioprotective, anti-inflammatory, and anticarcinogenic. Grape seed extract may be beneficial in a weight-management program. A paper (Moreno et al., 2003) reports that, in cultured adipocytes (fat cells), grape seed extract inhibited the fat-metabolizing enzymes pancreatic lipase, important for absorbing dietary fat, and lipoprotein lipase, which promotes fat storage. Orlistat, an FDA-approved drug for inhibiting fat absorption, also works by inhibiting lipases. The paper also notes that grape seed extract proanthocyanidins have been demonstrated to improve insulin sensitivity and/or to ameliorate the signs and symptoms of the metabolic syndrome. Another report (Del Bas et al., 2005) described gene expression in rats after giving them a single, high, nontoxic, oral dose of procyanidins (a subclass of proanthocyanidins) from GSPE (grape seed procyanidin extract). They found an increased expression of lipoprotein lipase in muscle, with decreased expression in adipose (fat) tissue. These changes, the authors explained, “strongly suggest the plasma TG [triglyceride] utilization in these animals is directed preferentially to energy production by the muscle instead of to energy storage by the adipose tissue. Thus, these short-term effects of GSPE on LPL [lipoprotein lipase] expression could lead, in the long term, to a reduced rate of weight gain, as has been described for animals consuming flavonoids in the diet.” [Citations deleted] Moreover, the authors (Del Bas et al., 2005) reported that triglyceride levels were reduced to 50% of the control group 5 hours after treatment. LDL-cholesterol was significantly lowered in GSPE groups, while HDL-cholesterol levels were slightly increased. Whereas HDL-C/LDL-C was increased, TC (total cholesterol)/HDL-C decreased in the GSPE-treated group. In cultured fat cells, grape seed extract inhibited enzymes that are important for absorbing dietary fat and promoting fat storage. Another paper (Preuss et al., 2002) reported a study where a combination of a niacin-bound chromium complex and a grape seed proanthocyanidin extract, or either one alone, resulted in reduced insulin levels in rats. Although glucose levels and glycosylated hemoglobin (a measure of longer-term blood glucose levels) were essentially similar to controls, the reduced insulin suggests improvement in insulin sensitivity. The same authors report that earlier studies of theirs demonstrated that niacin-bound chromium complex caused significant loss of body fat with sparing of muscle in overweight African-American women (Crawford et al., 1999). The authors also report improvements in LDL levels by a combination of niacin-bound chromium and grape seed extract in a study of 40 hypercholesterolemic patients. The latter study involved: niacin-bound chromium 200 mcg b.i.d. (intradermally twice daily); grape seed extract 100 mg b.i.d.; both together; or placebo. The greatest reduction of LDL occurred with the combination (–20% ± 6.0%). Other studies have reported improvements in blood glucose levels and insulin activity in streptozotocin-induced diabetic rats with grape seed extract supplementation (see, e.g., Pinent et al., 2004). Authors of a cell-culture study (Fujii et al., 2006) reported that grape seed polyphenols (especially their oligomers) had potent protective effects against high glucose-induced oxidative stress and that grape seed polyphenols also inhibited the activation of the proinflammatory cytokine NF-kappaB by high levels of glucose. Purple corn color’s beneficial properties include: (1) the ability to increase an important antiatherosclerotic molecule; (2) potent antioxidant activity; and (3) the ability to prevent obesity in mice on a high-fat diet. One particularly exciting study (Corder et al., 2004) reported that grape seed extract both improved endothelial-dependent vasodilator response and decreased the synthesis of endothelin-1, a potent vasoconstrictor, in isolated aorta preparations. As the authors point out, these effects are the same as those induced by laminar shear stress (the effect induced by nonturbulent flow of blood on endothelial cells lining blood vessels), an important antiatherosclerotic effect of laminar blood flow in arteries. They propose that the grape seed procyanidins may be pharmacological mimics of this natural protective effect, which is also a benefit of exercise. One more paper arrived today in our latest issue of the Journal of Agricultural and Food Chemistry. In this new study (Du et al., 2007), catechin and proanthocyanidin B4, two major polyphenolic compounds extracted from grape seeds, were found at low micromolar concentrations to induce antioxidant enzymes SOD (superoxide dismutase), catalase, GSH (glutathione), and GST (a phase 2 enzyme critically involved in the detoxification of reactive oxygen species). In addition, pretreatment of rat heart cells with catechin or proanthocyanidin B4 led to a marked reduction of xanthine oxidase-induced reactive oxygen species accumulation and heart cell apoptosis (programmed cell death). References Corder et al. The procyanidin-induced pseudo laminar shear stress response: a new concept for the reversal of endothelial dysfunction. Clin Sci (Lond) 107:513-7 (2004). Crawford et al. Effect of niacin-bound chromium supplementation on body composition in overweight African-American women. Diabetes Obes Metab 1:331-7 (1999). Del Bas et al. Grape seed procyanidins improve atherosclerotic risk index and induce liver CYP7A1 and SHP expression in healthy rats. FASEB J 19:479-81 (2005). Du et al. Grape seed polyphenols protect cardiac cells from apoptosis via induction of endogenous antioxidant enzymes J Agric Food Chem 55:1695-701 (2007). Fujii et al. Protective effect of grape seed polyphenols against high glucose-induced oxidative stress. Biosci Biotechnol Biochem 70(9):2104-11 (2006). Moreno et al. Inhibitory effects of grape seed extract on lipases. Nutrition 19:876-9 (2003). Pinent et al. Grape seed-derived procyanidins have an antihyperglycemic effect in streptozotocin-induced diabetic rats and insulinomimetic activity in insulin-sensitive cell lines. Endocrinology 145(11):4985-90 (2004). Preuss et al. Protective effects of a novel niacin-bound chromium complex and a grape seed proanthocyanidin extract on advancing age and various aspects of syndrome X. Ann NY Acad Sci 957:250-9 (2002). Purple Corn Color Purple corn is rich (about 70 mg/g) in the anthocyanin C3G (cyanidin-3-glucoside), which, having a beautiful purple color, is used extensively (about 50,000 kg of purple corn color per year) in Japan as a food color in confections and soft drinks. But while a purple color is esthetically pleasing, purple corn color has been found in scientific studies to have beneficial properties, including: (1) the ability to increase an important antiatherosclerotic molecule, adiponectin, which is reduced in the bloodstream of obese humans and mice and in insulin-resistant states (Tsuda, Ueno, et al., 2004) (in fact, when adiponectin was administered intravenously to mice fed high-fat/sucrose diets, weight gain was significantly inhibited); (2) potent antioxidant activity (Cevallos-Casals and Cisneros-Zevallos, 2003; Tsuda, Watanabe, et al., 1994; Kahkonen and Heinonen, 2003); and (3) the ability to prevent obesity in mice on a high-fat diet (Tsuda, Horio, Uchida, et al., 2003). In a 12-week study of the effects of C3G-rich purple corn color on obesity and hyperglycemia in mice (Tsuda, Horio, Uchida, et al., 2003), mice were fed a regular lab diet (controls) or: the regular diet plus purple corn color; the regular diet plus high fat; or the regular diet plus high fat plus purple corn color. The purple corn color supplement was added to diets at a C3G concentration of 2 g/kg of diet. One finding was that the mRNA of fatty acid synthase (the final enzyme in the synthesis of fat) was 81% lower in the high-fat-plus-purple-corn-color group (as compared to controls) and 57% lower than the high-fat group. While the high-fat diet increased the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) to 253.5 ± 41.9, as compared to 100 ± 5 (controls), the addition of purple corn color to the high-fat diet group resulted in a TNF-alpha level of 109.3 ± 14.0, which was not significantly different from the control level. TNF-alpha is strikingly increased in obesity and contributes to the increased risk of many diseases, such as atherosclerosis, to which the obese are prone. The study’s results on body weight showed that the control and high-fat-plus-purple-corn-color groups did not differ throughout the experimental period, whereas the high-fat group (without purple corn color) was significantly greater than the controls, the purple-corn-color group, and the high-fat-plus-purple-corn-color group from week 5 to 12. All the fat depots measured were markedly greater in the high-fat group than in the controls, whereas dietary purple corn color suppressed the high-fat-diet-induced increase in the adipose tissue depots. Adipose tissue weights in the high-fat-plus-purple-corn-color group did not differ from those in the control group. A final paper is worth describing. Here, some of the same authors who did much of the work reported above (Tsuda, Ueno, Yoshikawa, Kojo, Osawa, 2006) reported on a microarray-gene-expression profiling in human adipocytes treated with the anthocyanins C3G or Cy (cyanidin). They found a greater than 1.5-fold increase in the expression of adiponectin (improves insulin sensitivity) and a greater than 1.5-fold decrease in the expression of plasminogen activator inhibitor-1 (increased plasminogen activator inhibitor-1 is associated with both obesity and type 2 diabetes and promotes thrombosis). Another gene downregulated by more than 1.5-fold was IL-6, a cytokine secreted by adipocytes. It regulates acute-phase immune response and is elevated in obese and type 2 diabetes patients. Chronic IL-6 excess is associated with inflammation and has a detrimental effect on muscle strength (Maggio et al., 2006), and its administration to humans is reported to increase fasting plasma glucose levels. In one of our recent interviews, Sandy mentioned that we had significantly increased the amount of purple, blue, dark red, and black fruits, vegetables, and grains (to increase our consumption of anthocyanins). The above are some of the reasons! We are still looking for a source of purple sweet potato seeds to grow in our garden. If anyone knows a source, please let us know! The last two years, we grew a bumper crop of purple carrots.* Delicious! *Purple Dragon carrot seeds are available from John Scheepers Kitchen Garden Seeds, PO Box 638, Bantam, CT 06750 (860-567-6086) and other seed companies. References Cevallos-Casals and Cisneros-Zevallos. Stoichiometric and kinetic studies of phenolic antioxidants from Andean purple corn and red-fleshed sweet- potato. J Agric Food Chem 51:3313-9 (2003). Kahkonen and Heinonen. Antioxidant activity of anthocyanins and their aglycons. J Agric Food Chem 51:628-33 (2003). Maggio et al. Interleukin-6 in aging and chronic disease: a magnificent pathway. J Gerontol A Biol Sci Med Sci 61(6):575-84 (2006). Tsuda, Horio, Uchida, et al. Dietary cyanidin 3-O-beta-D-glucoside-rich purple corn color prevents obesity and ameliorates hyperglycemia in mice. J Nutr 133:2125-30 (2003). Tsuda, Ueno, et al. Anthocyanin enhances adipocytokine secretion and adipocyte-specific gene expression in isolated rat adipocytes. Biochem Biophys Res Commun 316:149-57 (2004). Tsuda, Ueno, Yoshikawa, Kojo, Osawa. Microarray profiling of gene expression in human adipocytes in response to anthocyanins. Biochem Pharmacol 71:1184-97 (2006). Tsuda, Watanabe, et al. Antioxidative activity of the anthocyanin pigments cyanidin 3-O-beta-D-glucoside and cyanidin. J Agric Food Chem 42:2407-10 (1994).