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    Default Increase IGF-1 Levels…Naturally!

    Reporter: “Arnold, what kind of milk do you drink?”
    Arnold: “I don't drink any milk. Milk is for babies. When you grow up, you drink beer.”


    Arnold didn’t drink milk, but he may have missed out on one of the most important muscle-building foods around. What makes milk so great? Milk is Mother Nature’s perfect supplement designed for babies to grow. A liter of milk contains 32 grams of protein coming from two main sources: casein and whey. These are without a doubt the two best proteins available. Milk is thought of as a “slow protein” for its ability to slowly be digested in the intestines, but milk can do a whole lot more. Recent studies in adult humans have consistently shown that high milk consumption is associated with a 10 percent to 20 percent increase in circulating IGF-1 levels in humans.10, 19-23 Even more interesting is that a head-to-head study comparing milk to meat as a protein source has shown that milk increases IGF-1 more profoundly than meat proteins. Before I dive into the research, here is a brief summary of IGF-1 basics and why increasing IGF-1 levels are important for increasing muscle mass

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    IGF-1: Anabolic And Anti-Catabolic
    A number of studies have associated age-related declines in circulating anabolic factors, including IGF-1 and testosterone, with the muscle atrophy of aging, suggesting that these serum factors are important for the maintenance of muscle mass. Scientists wanted to see what would happen to muscle satellite cells of older mice if they restored their serum levels of IGF-1 to those of young mice. Using a parabiosis model (a parabiosis model surgically attaches the circulatory system of two animals…in this case, an older and a younger mouse), these researchers showed that the circulating IGF-1 plays an important role in the regenerative capabilities of skeletal muscle, including satellite cell recruitment, as regenerative capacity was restored in aged mice provided a young circulation.33 This study clearly shows that satellite cells of aging muscle are influenced by serum levels of IGF-1, as chronic exposure to serum from young animals restored the regenerative capacities of satellite cells in old mice. Furthermore, exogenous IGF-1 applied to atrophied muscles in rats has been shown to significantly increase muscle mass and satellite cell activity.


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    Protein Influences IGF-1 Concentrations
    Concentrations of IGF-1 appear to be influenced by total calories, protein intake and certain micronutrients (potassium, magnesium and zinc), as shown in both animal and human studies.3 It has been reported that the nutritional status, not only energy and amino acid restriction, are critical regulators of IGF-1. For example, one study examined the effect of protein or carbohydrate supplementation in conjunction with strength and conditioning training on IGF-1 over a six-month period. The results of this study indicated that a protein supplement consumed during a strength and conditioning program led to an increase in plasma concentrations of IGF-1 in those subjects compared with the concentrations in a group of persons who also trained, but consumed a calorically equivalent carbohydrate supplement.27 Endurance runners represent the perfect diet model for how diet modifies IGF-1. Endurance runners who consume a diet low in protein yet high in carbohydrates have lower IGF-1 levels compared to sedentary adults consuming a Western diet, which was high in protein and calories.15 This in conjunction with other studies that have also found a substantial depressing effect of a persistently used low-protein diet on circulating total and free IGF-1. A certain amount of protein and carbohydrates are needed for IGF-1, but the traditional high-protein/low-carbohydrate diet bodybuilders follow causes a drop in serum levels of IGF-1 and insulin; however, muscle gene expression of IGF-1 actually increases.34


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    Got IGF-1?
    Most bodybuilders know that milk contains casein and is known as a slow protein for its unique ability to coagulate in the small intestines and release slowly into the bloodstream. Approximately 80 percent of the protein in cow’s milk is casein and the remaining 20 percent is whey. Casein proteins clot in low-pH solutions. Hence, the acidity in the stomach makes casein clump into a gel, whereas whey remains soluble. Both whey and casein contain specific proteins and peptides that may have growth-stimulating effects. Additionally, the degradation of milk proteins when they are exposed to the acid in the stomach results in many other peptides that also may have specific effects.

    Casein May Protect IGF-1 Degradation
    More than just proteins, milk contains many other growth-enhancing components. Milk also contains growth factors, prostaglandins, insulin and other neuropeptides. Although it is unknown which components in milk may be responsible for stimulating the IGFs, it is currently speculated that bioactive peptides, milk IGF-1, Amino Acids or milk minerals are involved. It has long been thought that many of the hormones and growth factors in milk are destroyed by the pasteurization process of milk and that the little bioactive hormones that are still present are destroyed by liver metabolism. Some researchers speculate that some of those growth factors may indeed be surviving the digestive process and increasing circulating IGF-1 levels. For example, rats fed cow’s milk (1 percent, low fat) had higher levels of IGF-1 than those rats fed dry, powdered milk even though total calories and protein were the same.24 How is this possible? A couple of studies have shown that radioactively labeled IGF-1 have demonstrated intact oral absorption and plasma bioavailability when IGF-1 is administered with the casein, the primary component in milk. If IGF-1 is surviving the pasteurization and digestive process, some of the bioactive growth factors such as IGF-1 may make it into circulation


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    Milk Increases IGF-1
    Several studies have reported that high milk intake results in higher serum IGF-1 levels.2 Cow’s milk contains IGF-1 that is structurally identical to human IGF-1.11 Despite this, it is generally thought that IGF-1 will not retain bioactivity when delivered orally because it is rapidly destroyed by the digestive system. This is supported by results from a study that showed orally administrated IGF-1 was poorly absorbed.12 Nevertheless, in a study on adult rats, it was shown that some IGF antibodies and dietary protein casein may protect the IGF-1 from degradation in the gastrointestinal tract and increase plasma levels.13 Dairy foods other than milk (ice cream, yogurt and cheese) do not increase levels of IGF-1, which may be due to the fermentation process. It is possible that either IGF-1 in cows’ milk or a substance in milk that stimulates endogenous production of IGF-1 is inactivated during the processing of milk to ice cream, yogurt or cheese. Here are some interesting studies to think about:

    • A randomized study among 204 adult men and women reported that those who consumed three 8-ounce servings per day of nonfat or 1 percent milk for 12 weeks had a 10 percent increase in serum IGF-1 levels compared to individuals who didn’t drink milk.5
    • In a six-month, randomized, placebo-controlled trial, 80 elderly patients with a recent hip fracture received either a 20-gram per day protein supplement, composed of 90 percent milk protein or an isocaloric placebo. A significant increase of circulating IGF-1 was found in the milk group compared with the placebo group.6
    • In more than 1,000 participants, a positive association between protein intake and circulating IGF-1 concentrations was found and the increased IGF-1 concentrations was largely attributable to milk intake.7
    • In a study of 344 healthy, middle-aged men, milk intake was positively associated with raised levels of IGF-1. Men in the lowest milk intake (<1/2 pint/day) had significantly lower values of circulating IGF-1 than those in the middle (1/2–3/4 pint/day) and highest (1+pint/day) tertiles.8
    • In a Danish study of small children, increasing milk intake from 200 to 300 m/L per day corresponded with a 30 percent increase in circulating IGF-1.18


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    Milk…It’s Not Just For Babies!
    Many studies have shown that high intakes of protein are associated with increases in insulin and IGF-1. Several Amino Acids are potent stimulators of insulin release when taken as a protein orally and certain Amino Acids (branched-chain Amino Acids or BCAAs) are more insulinogenic (increasing insulin) than are others. It has been shown that the insulin response in healthy subjects was positively correlated with plasma leucine, phenylalanine and tyrosine when ingested orally in the form of drinks in combination with glucose.29 BCAAs (leucine, isoleucine and valine) are suggested to stimulate secretion of insulin and thereby increase serum IGF-1 levels, but there is something in milk that increases IGF-1 greater than other proteins. In a one-week intervention study of 24 young boys, the effect of milk or meat intake on IGF-1 was examined. The boys were asked to consume either 1.5 liters of skim milk daily or the same amount of animal protein as low-fat meat. They were free to choose the rest of their diet. The high intake of milk increased concentrations of IGF-1 by 19 percent. There were no increases in IGF-1 in the meat group. Thus, a high intake of milk, and not a high intake of meat, increased the concentrations of serum IGF-1.4


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    Milk Has A Low Glycemic Index, But A High Insulinemic Index
    We may be overlooking a very obvious fact about milk— it has a high insulinemic effect. In a study based on regular milk and yogurt products, a discrepancy between glycemic index (GI) and insulinemic index was found; despite very low GIs (15-30), a high insulinemic index was found (90-98) for both milk and yogurt.25 For example, one study compared glucose and insulin responses of dry, powdered milk and whole milk to white bread. Although the blood glucose response after the test meals with reconstituted skim milk powder was low, the insulin response after whole milk was not significantly distinguishable from that after the white bread. Thus, pasteurized milk resulted in a discrepancy between blood glucose (GI=30) and the insulin response (II=90). The insulinotropic effect was not related only to the carbohydrate component of milk, but also to some yet unidentified food component.
    It may be the high insulin response that results in higher IGF-1 responses than meat proteins. One study comparing meat to milk insulin responses reported that a high intake of milk more than doubled fasting serum insulin concentrations. In the meat group, however, there was no increase in insulin. Interestingly, the concentration of BCAAs increased similarly in the two groups. Another study compared insulin and glucose responses of fish to milk protein. There was a significantly larger insulin response for subjects consuming milk protein rather than cod protein, especially after the first hour. Additionally, there were higher insulin/glucose ratios in the subjects after the milk protein meal compared to the fish protein meal. The predominant Amino Acids in fish protein are lysine, methionine and alanine, whereas in casein, it’s glutamine acid, isoleucine, leucine, valine, proline, tyrosine and histidine. As earlier stated, the BCAAs isoleucine, leucine and valine are suggested to be most closely related to the insulin response, which could explain that milk protein with a high amount of these Amino Acids gives a higher insulin response.


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    Caffeine: Another Way Of Increasing IGF-1 Levels?
    In addition to milk and a high-protein diet, it seems that caffeine may also increase IGF-1 levels. It has been shown that coffee consumption reduces the incidence of type 2 diabetes; new research suggests that caffeine may increase the IGF-1-signaling pathway. After a 12-week administration of 0.01 percent caffeine solution to diabetic rats, the rats exhibited reduced bodyweight, fats and insulin resistance without a change in food intake. In addition, caffeine enhanced insulin secretion. The insulinotropic action of caffeine was explained by enhanced IGF-1-signaling cascade. These findings indicate that long-term caffeine consumption can help alleviate diabetic symptoms by enhancing insulin sensitivity through improved insulin/IGF-1 signaling.14 Two large-scale studies did find that higher levels of IGF-1 were associated with higher coffee consumption, but more studies are needed.30, 31


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    Hold The Tomatoes On My Burger….I Am Trying To Get Big!
    Recent studies have shown that subjects consuming diets rich in tomato-containing products or lycopene had lower circulating levels of IGF-1.17 It has been shown that taking a lycopene extract or high levels of tomato-rich products can decrease IGF-1 levels, but moderate consumption of lycopene consumption has no effect. For example, drinking 1 cup of tomato juice has no effect on IGF-1 levels, while lycopene extracts seems to depress IGF-1 levels. The mechanism by which tomato carotenoids alter IGF status is not clear. The reduction in IGF-1 concentration by antiestrogens is the strongest evidence for the involvement of estrogens in this system. Interestingly, it has been found that various tomato carotenoids interfere in estrogen signaling, which suggests that this may be one of the mechanisms for the reduction of the IGF-1 level.


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    Key Points:

    • IGF-1 is a powerful anabolic/anti-catabolic hormone.
    • Milk has a low glycemic index, but a high insulinemic index.
    • Large-scale studies have shown that higher milk consumption is associated with higher IGF-1 levels.
    • Milk consumption increases IGF-1 levels through many possible pathways (Amino Acids, minerals, IGF-1 in milk, insulin).
    • Caffeine may increase IGF-1.
    • Large amounts of lycopene consumption or lycopene extracts can decrease IGF-1

    References:

    1. Bark, TH, McNurlan, MA, Lang, CH, Garlick, PJ. Increased protein synthesis after acute IGF-1 or insulin infusion is localized to muscle in mice. Am J Physiol, 275(1 Pt 1):E118-23, 1998.
    2. Morimoto LM, Newcomb PA, White E, Bigler J, Potter JD. Variation in plasma insulin-like growth factor-1 and insulin-like growth factor-binding protein-3: personal and lifestyle factors (United States). Cancer Causes Control, 2005 Oct;16(8):917-27.
    3. Ninh NX, Thissen JP, Collette L, Gerard G, Khoi HH, Ketelslegers JM. 1996. Zinc supplementation increases growth and circulating insulin-like growth factor 1 (IGF-1) in growth-retarded Vietnamese children. Am J Clin Nutr, 63:514–19.
    4. Hoppe C, Mølgaard C, Juul A, Michaelsen KF. 2004. High intakes of skimmed milk, but not meat, increase serum IGF-1 and IGFBP-3 in eight-year-old boys. Eur J Clin Nutr, 58:1211–16.
    5. Heaney RP, McCarron DA, Dawson- Hughes B, Oparil S, Berga SL, et al. 1999. Dietary changes favorably affect bone remodeling in older adults. J Am Diet Assoc, 99:1228–33.
    6. Schurch MA, Rizzoli R, Slosman D, Vadas L, Vergnaud P, Bonjour JP. 1998. Protein supplements increase serum insulin-like growth factor-I levels and attenuate proximal femur bone loss in patients with recent hip fracture. A randomized, double-blind, placebo-controlled trial. An Intern Med, 128:801–9.
    7. Holmes MD, Pollak MN, Willett WC, Hankinson SE. 2002. Dietary correlates of plasma insulin-like growth factor 1 and insulin-like growth factor-binding protein-3 concentrations. Cancer Epidemiol Biomarkers Prev, 11:852–61.
    8. Gunnell D, Oliver SE, Peters TJ, Donovan JL, Persad R, et al. 2003. Are diet/prostate cancer associations mediated by the IGF axis? A cross-sectional analysis of diet, IGF-1 and IGF-BP-3 in healthy, middle-aged men. Br J Cancer, 88:1682–86.
    9. Ma J, Giovannucci E, Pollak M, Chan JM, Gaziano JM, et al. 2001. Milk intake, circulating levels of insulin-like growth factor-1 and risk of colorectal cancer in men. J Natl Cancer Inst, 93:1330–36.
    10. Hoppe C, Mølgaard C, Vaag A, Michaelsen KF. 2006. The effect of seven-day supplementation with milk protein fractions and milk minerals on IGFs and glucose-insulin metabolism. Scand J Food Nutr, 50:46.
    11. Daxenberger A, Breier BH, Sauerwein H. 1998. Increased milk levels of insulin-like growth factor 1 (IGF-1) for the identification of bovine somatotropin-treated cows. Analyst, 123:2429–35.
    12. Donovan SM, Chao JC, Zijlstra RT, Odle J. 1997. Orally administered iodinated recombinant human insulin-like growth factor-1 (125I-rhIGF-1) is poorly absorbed by the newborn piglet. J Pediatr Gastroenterol Nutr, 24:174–82.
    13. Xian CJ, Shoubridge CA, Read LC. 1995. Degradation of IGF-1 in the adult rat gastrointestinal tract is limited by a specific antiserum or the dietary protein casein. J Endocrinol, 146:215–25.
    14. Park S, Jang JS, Hong SM. Long-term consumption of caffeine improves glucose homeostasis by enhancing insulinotropic action through islet insulin/insulin-like growth factor-1 signaling in diabetic rats. Metabolism, 2007 May;56(5):599-607.
    15. Quinn LS, Anderson BG, Plymate SR. Muscle-specific overexpression of the type-1 IGF receptor results in myoblast-independent muscle hypertrophy via PI3-K and not calcineurin signaling. Am J Physiol Endocrinol Metab, 2007 Oct 16.
    16. Fontana L, Klein S, Holloszy JO. Long-term low-protein, low-calorie diet and endurance exercise modulate metabolic factors associated with cancer risk. Am J Clin Nutr, 2006 Dec;84(6):1456-62.
    17. Walfisch S, Walfisch Y, Kirilov E, Linde N, Mnitentag H, Agbaria R, Sharoni Y,Levy J. Tomato lycopene extract supplementation decreases insulin-like growth factor-1 levels in colon cancer patients. Eur J Cancer Prev, 2007 Aug;16(4):298-303.


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    18. Riso P, Brusamolino A, Martinetti A, Porrini M. Effect of a tomato drink intervention on insulin-like growth factor (IGF)-1 serum levels in healthy subjects. Nutr Cancer, 2006;55(2):157-62.
    19. Ma J, Giovannucci E, Pollak M, Chan JM, Gaziano JM, Willett W, Stampfer MJ: Milk intake, circulating levels of insulin-like growth factor-1, and risk of colorectal cancer in men. J Natl Cancer Inst, 2001, 93:1330-1336.
    20. Giovannucci E, Pollak M, Liu Y, Platz EA, Majeed N, Rimm EB, Willett WC: Nutritional predictors of insulin-like growth factor 1 and their relationships to cancer in men. Cancer Epidemiol Biomarkers Prev, 2003, 12:84-89.
    21. Holmes MD, Pollak MN, Willett WC, Hankinson SE: Dietary correlates of plasma insulin-like growth factor 1 and insulin-like growth factor-binding protein-3 concentrations. Cancer Epidemiol Biomarkers Prev, 2002, 11:852-861.
    22. Hoppe C, Udam TR, Lauritzen L, Molgaard C, Juul A, Michaelsen KF: Animal protein intake, serum insulin-like growth factor 1 and growth in healthy 2.5-y-old Danish children. Am J Clin Nutr, 2004, 80:447-452.
    23. Hoppe C, Mølgaard C, Juul A, Michaelsen KF: High intakes of skimmed milk, but not meat, increase serum IGF-1 and IGF-BP-3 in 8-year-old boys. European Journal of Clinical Nutrition, 2004.
    24. Heaney RP, McCarron DA, Dawson-Hughes B, Oparil S, Berga SL, Stern JS, Barr SI, Rosen CJ: Dietary changes favorably affect bone remodeling in older adults. J Am Diet Assoc, 1999, 99:1228-1233.
    25. Qin LQ, Xu JY, Wang PY, Ganmaa D, Li J, Wang J, Kaneko T, Hoshi K, Shirai T, Sato A: Low-fat milk promotes the development of 7,12-dimethylbenz(A)anthracene (DMBA)-induced mammary tumors in rats. Int J Cancer, 2004, 110:491-496.
    26. Liljeberg EH & Bjorck I (2001): Milk as a supplement to mixed meals may elevate postprandial insulinemia. Eur J Clin Nutr, 55, 994–999.
    27. Ballard TL, Clapper JA, Specker BL, Binkley TL, Vukovich MD. Efect of protein supplementation during a 6-mo strength and conditioning program on insulin-like growth factor 1 and markers of bone turnover in young adults. Am J Clin Nutr, 2005 Jun;81(6):1442-8.
    28. Voskuil DW, Vrieling A, van't Veer LJ, Kampman E, Rookus MA. The insulin-like growth factor system in cancer prevention: potential of dietary intervention strategies. Cancer Epidemiol Biomarkers Prev, 2005 Jan;14(1):195-203. Review.
    29. van Loon LJ, Saris WH, Verhagen H, Wagenmakers AJ. Plasma insulin responses after ingestion of different amino acid or protein mixtures with carbohydrate. Am J Clin Nutr, 2000 Jul;72(1):96-105.
    30. Signorello LB, Kuper H, Lagiou P, Wuu J, Mucci LA, Trichopoulos D, Adami HO. Lifestyle factors and insulin-like growth factor 1 levels among elderly men. Eur J Cancer Prev, 2000 Jun;9(3):173-8.
    31. Landin-Wilhelmsen K, Lundberg PA, Lappas G, Wilhelmsen L. Insulin-like growth factor 1 levels in healthy adults. Horm Res, 2004;62 Suppl 1:8-16.
    32. von Post-Skagegard M, Vessby B, Karlstrom B. Glucose and insulin responses in healthy women after intake of composite meals containing cod, milk and Soy protein. Eur J Clin Nutr, 2006 Aug;60(8):949-54.
    33. Conboy IM, Conboy MJ, Wagers AJ, Girma ER, Weissman IL, Rando TA. Rejuvenation of aged progenitor cells by exposure to a young systemic environment. Nature, 2005 Feb 17;433(7027):760-4.
    34. Harber MP, Schenk S, Barkan AL, Horowitz JF. Effects of dietary carbohydrate restriction with high protein intake on protein metabolism and the somatotropic axis. J Clin Endocrinol Metab, 2005 Sep;90(9):5175-81.


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