Expert: Glen Aukerman, M.D. - 1/5/2008

Question
hi

i have a pituitary tumor, is there a way to lower the igf-1 naturally

also how to you get rid of ascites naturally

thanks so much

Answer
We use omega-3 to do this after we balance the nutrition at our center, see www.medicalcenter.osu.edu/go/integrative

Below are a few abstracts supporting the use of omega-3 but remember flax is not useable by humans to any significant degree.

1: Nutrition. 2006 Jul-Aug;22(7-8):713-21.Related Articles, Links   
Effects of long-term continuous use of immune-enhancing enteral formula on nutritional and immunologic status in non-surgical patients.

Sakurai Y, Oh-Oka Y, Kato S, Suzuki S, Hayakawa M, Masui T, Yoshida I, Tonomura S, Mitsutaka S, Nakamura Y, Uyama I, Komori Y, Ochiai M.

Department of Surgery, Fujita Health University School of Medicine, Toyoake, Aichi, Japan; Okazaki Mita Hospital, Ozaki, Aichi, Japan. ysakurai@fujita-hu.ac.jp

OBJECTIVE: Although the perioperative use of immune-enhancing enteral formula (IEEF) effectively reduces the rate of infectious complications, whether chronic use of IEEF is beneficial is unknown. A prospective randomized clinical trial was performed to examine the safety and effectiveness of long-term IEEF on nutritional and immunologic status in non-surgical patients receiving total enteral nutrition through the gastrostomy access route. METHODS: A total of 30 patients were randomly assigned to two groups in which they received total enteral nutrition, an IEEF (n = 15) or a regular polymeric enteral formula (control group; n = 15) for 12 wk. Nutritional and immunologic variables were periodically examined. RESULTS: Serum concentrations of insulin-like growth factor-I increased significantly for the IEEF group throughout the study. Although serum concentrations of dihomo-gamma-linoleic acid decreased significantly in the IEEF group, serum concentrations of eicosapentaenoic acid and docosahexaenoic acid increased significantly, as did concentrations of serum arginine and ornithine. The CD4/CD8 ratio and natural killer cell activity also increased for the IEEF group, but the differences were not significant. The B-cell fraction increased and the T-cell fraction of peripheral lymphocytes decreased for the IEEF group. Neither infectious nor non-infectious complications occurred during the study period in either group, except for a significant increase in serum urea nitrogen and uric acid concentrations for the IEEF group. CONCLUSION: Long-term use of IEEF is safe in non-surgical patients and results in a significant increase in serum insulin-like growth factor-I concentrations in association with increased humoral immunity.

Publication Types:
Randomized Controlled Trial

PMID: 16815486 [PubMed - indexed for MEDLINE]

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2: J Nutr. 2005 Mar;135(3):505-12.Related Articles, Links  
Low levels of dietary arachidonic and docosahexaenoic acids improve bone mass in neonatal piglets, but higher levels provide no benefit.

Mollard RC, Kovacs HR, Fitzpatrick-Wong SC, Weiler HA.

Department of Human Nutritional Sciences, University of Manitoba, Winnipeg, Manitoba, R3T 2N2 Canada.

In piglets, feeding arachidonic acid (AA) and docosahexaenoic acid (DHA) in a 5:1 ratio leads to elevated bone mass, but the optimal total quantity requires clarification. We studied bone mass and modeling of piglets that were randomized to receive 1 of 4 formulas for 15 d: control formula or the same formula with various levels of AA:DHA (0.5:0.1 g, 1.0:0.2 g or 2.0:0.4 g AA:DHA/100 g of fat). Measurements included: bone area (BA), mineral content (BMC), and density (BMD) of whole body, lumbar spine, and excised femurs; biomarkers of bone modeling were plasma osteocalcin and urinary cross-linked N-telopeptides of type 1 collagen (NTx), tibial ex vivo release of prostaglandin E(2) (PGE(2)), plasma insulin-like growth factor-1 (IGF-1), and tissue fatty acids. Main effects were identified using ANOVA and post hoc Bonferroni t tests. In supplemented piglets, relations among liver fatty acid proportions and bone mass were assessed using Pearson correlations. Whole body (P = 0.028) and lumbar spine (P = 0.043) BMD were higher in the group supplemented with 0.5:0.1 g AA:DHA/100 g of fat than in controls. Tissue AA and DHA increased in proportion to diet levels. Liver eicosapentaenoic acid (EPA) correlated positively (r > or = 0.38, P < or = 0.05) with whole body and femur BMC and BMD and lumbar spine BMC. Liver AA:EPA ratio correlated negatively (r > or = -0.039, P < or = 0.05) with whole body, femur, and lumbar spine BMC plus whole body and femur BMD. Dietary 1.0:0.2 g AA:DHA/100 g reduced NTx relative to 2.0:0.4 g AA:DHA/100 g of fat (P = 0.039). The diets did not affect the other biochemical variables measured. Low levels of dietary AA:DHA (0.5:0.1 g/100 g of fat) elevate bone mass, but higher amounts are not beneficial.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 15735085 [PubMed - indexed for MEDLINE]

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3: Cancer Epidemiol Biomarkers Prev. 2003 Aug;12(8):739-46.Related Articles, Links  
Determinants of circulating insulin-like growth factor I and insulin-like growth factor binding protein 3 concentrations in a cohort of Singapore men and women.

Probst-Hensch NM, Wang H, Goh VH, Seow A, Lee HP, Yu MC.

University Hospital Zürich, Cancer Registry Zürich, Zürich, Switzerland. nicole.probst@ifspm.unizh.ch

Variation in the circulating concentrations of the insulin-like growth factor (IGF) system has been implicated in the etiology of chronic diseases including cancer (prostate, breast, colon, and lung), heart disease, type 2 diabetes, and osteoporosis. We searched for sociodemographic, anthropometric, reproductive, lifestyle, and dietary determinants of IGF-I and insulin-like growth factor binding protein (IGFBP) -3 serum concentrations. Serum samples were collected in a Singapore Chinese cohort with a mean age of 61 years. Subject information was assessed during an in-person interview. Radioimmunometrically measured IGF-I and IGFBP-3 concentrations were available for 312 men and 326 postmenopausal women ages 50 years or older. Mean IGF-I concentrations were 144 ng/ml and 121 ng/ml for men and women, respectively (gender difference, P < 0.0001), and mean IGFBP-3 concentrations were 3710 ng/ml and 4147 ng/ml for men and women, respectively (gender difference, P < 0.0001). IGF-I and IGFBP-3 decreased with age (P for trend <0.0001); the age-related decrease in the IGF-I:IGFBP-3 molar ratio was stronger in women than men. IGF-I concentrations were higher among physically inactive subjects and among women with an early age at menarche. Consumption of saturated fat was found to decrease, and intake of omega-3 polyunsaturated fatty acids and of dietary fiber was found to increase circulating IGFBP-3 concentrations. Intake of calcium from food and supplement was associated positively with circulating IGF-I, IGFBP-3, and molar ratio. Intake of soy was associated positively with IGF-I and molar ratio concentrations, but only in men. The results of this study lend additional support to the hypothesis that circulating IGF-I concentrations increase the risk of prostate, bladder, colorectal, and breast cancer.

Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

PMID: 12917205 [PubMed - indexed for MEDLINE]

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4: Hypertension. 2003 Sep;42(3):342-8. Epub 2003 Jul 21.Related Articles, Links  
Eicosapentaenoic acid protects endothelial cells against anoikis through restoration of cFLIP.

Suzuki T, Fukuo K, Suhara T, Yasuda O, Sato N, Takemura Y, Tsubakimoto M, Ogihara T.

Department of Geriatric Medicine, Osaka University Medical School, Suita, Osaka, Japan.

Dietary supplementation with eicosapentaenoic acid (EPA) improves the prognosis of chronic inflammatory diseases, including atherosclerosis. The mechanism underlying these beneficial effects, however, remains to be elucidated. Here we show that EPA protects endothelial cells from anoikis through upregulation of the cellular FLICE (Fas-associating protein with death domain-like interleukin-1-converting enzyme)-inhibitory protein (cFLIP), an endogenous inhibitor of caspase-8. EPA-induced upregulation of cFLIP expression was partially suppressed by the phosphatidylinositol-3-kinase inhibitor wortmannin. Conversely, treatment with insulinlike growth factor-1 (IGF-1), an activator of phosphatidylinositol-3-kinase/Akt signaling, or infection with an adenoviral construct expressing the constitutively active Akt gene induced upregulation of cFLIP expression. In addition, pretreatment of endothelial cells with either EPA or IGF-1 protected them from anoikis, suggesting that EPA-induced protection against anoikis is partially mediated through activation of Akt. On the other hand, when endothelial cells were already detached, treatment of these cells with EPA but not with IGF-1 protected them against anoikis. Importantly, EPA restored cFLIP expression without activating Akt signaling in detached endothelial cells, whereas IGF-1 had no effect. Additionally, exogenously restored expression of cFLIP by the tetracycline-regulated adenovirus system protected endothelial cells against anoikis. Furthermore, EPA was protective against the loss of endothelium in an organ culture of rat aortas. These findings suggest that EPA protects against endothelial cell anoikis through restoration of cFLIP expression, which might contribute to the mechanism underlying the beneficial effects of EPA in patients with hypertension.

PMID: 12874095 [PubMed - indexed for MEDLINE]

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5: Med Hypotheses. 2003 Jul;61(1):1-15.Related Articles, Links   
A wholly nutritional 'multifocal angiostatic therapy' for control of disseminated cancer.

McCarty MF.

Pantox Laboratories, San Diego, California 92129, USA.

A great deal of effort is now being devoted to the development of new drugs that hopefully will control the spread of inoperable cancer by safely inhibiting tumor-evoked angiogenesis. However, there is growing evidence that certain practical nutritional measures have the potential to slow tumor angiogenesis, and it is reasonable to anticipate that, by combining several measures that work in distinct but complementary ways to impede the angiogenic process, a clinically useful 'multifocal angiostatic therapy' (MAT) might be devised. Several measures which might reasonably be included in such a protocol are discussed below, and include: a low-fat, low-glycemic index vegan diet, which may down-regulate the systemic IGF-I activity that supports angiogenesis; supplemental omega-3-rich fish oil, which has been shown to inhibit endothelial expression of Flk-1, a functionally crucial receptor for VEGF, and also can suppress tumor production of pro-angiogenic eicosanoids; high-dose selenium, which has recently been shown to inhibit tumor production of VEGF; green tea polyphenols, which can suppress endothelial responsiveness to both VEGF and fibroblast growth factor; and high-dose glycine, whose recently reported angiostatic activity may reflect inhibition of endothelial cell mitosis, possibly mediated by activation of glycine-gated chloride channels. In light of evidence that tumor-evoked angiogenesis has a high requirement for copper, copper depletion may have exceptional potential as an angiostatic measure, and is most efficiently achieved with the copper-chelating drug tetrathiomolybdate. If logistical difficulties make it difficult to acquire this experimental drug, high-dose zinc supplementation can achieve a slower depletion of the body's copper pool, and in any case can be used as maintenance therapy to maintain an adequate level of copper depletion. A provisional protocol is offered for a nutritionally based MAT entailing a vegan diet and supplemental intakes of fish oil, selenium, green tea polyphenols, glycine, and zinc. Inasmuch as cox-2 is overexpressed in many cancers, and cAMP can boost tumor production of various angiogenic factors as well as autogenous growth factors, adjunctive use of cox-2-specific NSAIDS may be warranted in some cases.

PMID: 12781633 [PubMed - indexed for MEDLINE]

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6: Horm Res. 2002;58 Suppl 1:16-20.Related Articles, Links  
Nutrition and growth in cystic fibrosis.

Hankard R, Munck A, Navarro J.

Clinical Investigation Unit, Robert Debré Hospital, Paris, France. regis.hankard@rdb.ap-hop-paris.fr

Malnutrition is a common complication of chronic diseases in children and may lead to growth impairment (stunting). Malnutrition in cystic fibrosis (CF) results from increased energy expenditure, decreased energy intakes, malabsorption of ingested nutrients because of pancreatic insufficiency and chronic inflammation. Malnutrition and high levels of inflammatory cytokines affect IGF-1 production through interrelated mechanisms. Nutritional support was shown to improve both nutritional status and outcome in CF. However, some nutrients have a direct effect on the disease. n-3 fatty acids supplementation is able to correct lipid abnormalities resulting from a primary mechanism. Moreover, n-3 fatty acids have a direct effect on the inflammatory response, decreasing eicosanoid synthesis and modulating nuclear transcriptional factors nuclear factor kappaB and peroxisome proliferator-activated receptors gamma. Nutritional support may be considered part of the care of the CF patient together with antibiotics, pancreatic enzymes and physiotherapy, influencing significantly the evolution of the disease. Copyright 2002 S. Karger AG, Basel

Publication Types:
Review

PMID: 12373008 [PubMed - indexed for MEDLINE]

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7: Crit Care Med. 2000 Jul;28(7):2366-72.Related Articles, Links  
Decreased serum insulin-like growth factor-I in burn patients: relationship with serum insulin-like growth factor binding protein-3 proteolysis and the influence of lipid composition in nutritional support.

Abribat T, Nedelec B, Jobin N, Garrel DR.

Burn Centre, Hotel-Dieu Hospital, Montréal, Québec, Canada.

OBJECTIVES: To test the effects of the amount and type of fat in the nutritional support on serum insulin-like growth factor (IGF)-I concentrations in burn patients and to test the hypothesis that the serum proteolytic activity for insulin-like growth factor binding protein (IGFBP)-3 is a major mechanism for the decreased serum IGF-I observed in these patients. DESIGN: Randomized, double-blind trial of three different nutritional supports and analysis of serum IGF-I, IGFBP-3, and serum IGFBP-3 proteolysis. SETTING: Burn center in a university hospital. PATIENTS: A total of 23 severely burned (>25% total body surface area burned) adult patients. INTERVENTIONS: Patients were randomly assigned to three types of nutritional support differing in the amount of energy derived from fat and the presence or absence of fish oil: Group I (control), 35% fat; Group II, 15% fat; Group III, 15% fat with 50% as fish oil. Nutritional support was both parenteral and enteral and was started within 24 hrs of admission. MEASUREMENTS AND MAIN RESULTS: Serum IGF-I and IGFBP-3 were measured by radioimmunoassay every 3 days for 28 days in 23 severely burned adults. In six patients, IGFBP-3 was measured by ligand binding assay and the serum proteolytic activity for rhIGFBP-3 was measured as well. Serum IGF-I concentration was low in all subjects throughout the study period, but did increase with time (p < .01); significantly higher values were found in Group III (p < .05). Multivariate analysis showed that fish oil and low fat solutions were significantly correlated to serum IGF-I concentrations. Serum IGFBP-3 (radioimmunoassay) was higher than normal throughout the study with no difference between the groups. Between days 4 and 16, IGFBP-3 was cleaved into two fragments in all patients studied, and the molecular weights of the fragments were equal to those observed in the serum of a woman late in pregnancy. During this period of time, serum proteolytic activity for rhIGFBP-3 was >30% in 24 of the 30 samples measured, whereas 20 of the 28 samples measured thereafter were normal (<25%). Serum IGFBP-3 concentration from ligand binding assay was correlated with serum proteolytic capacity in all subjects (mean r2 = 0.77; p < .01) and with serum IGF-I concentrations in five of six subjects (mean r2 = 0.81; p < .01). CONCLUSIONS: In burn injury, serum IGF-I concentrations are sensitive to the amount and type of fat in their nutritional support. The presence of fish oil allowed for a more rapid recovery of serum IGF-I levels. The proteolysis of IGFBP-3 may be an important cause of the decreased serum IGF-I values and the protease(s) responsible for this seem to be similar to those observed in late pregnancy.

Publication Types:
Clinical Trial
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

PMID: 10921566 [PubMed - indexed for MEDLINE]

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8: J Lipid Mediat Cell Signal. 1997 Jul;16(3):189-97.Related Articles, Links   
Supplementation of MCF-7 cells with essential fatty acids induces the activation of protein kinase C in response to IGF-1.

Lanson M, Besson P, Bougnoux P.

J.E. 313 Lipides et croissance, Faculté de Médecine, Tours, France.

The effects of changing the composition of membrane lipids on protein kinase C (PKC) activation were studied in MCF-7 human breast cancer cells. The supply of linoleate or alpha-linolenate to MCF-7 cells altered cell membranes fatty acid composition but did not affect PKC activity. When the cells were additionally exposed to IGF-1, the same fatty acids caused a dramatic increase in membrane-bound PKC activity. We also found that the mitogenic response induced by IGF-1 was not enhanced in those conditions when PKC becomes activated by linoleate and alpha-linolenate. These data show that these fatty acids elicit a distinct route for the transmission of IGF-1 signal by inducing the PKC pathway. They suggest that linoleate and alpha-linolenate could control the biological response of MCF-7 cells to IGF-1.

PMID: 9246607 [PubMed - indexed for MEDLINE]

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9: Am J Clin Nutr. 1991 Oct;54(4):684-8.Related Articles, Links
Effects of omega 3 fatty acids and vitamin E on hormones involved in carbohydrate and lipid metabolism in men.

Bhathena SJ, Berlin E, Judd JT, Kim YC, Law JS, Bhagavan HN, Ballard-Barbash R, Nair PP.

Carbohydrate Nutrition Laboratory, BHNRC, USDA, MD 20705.

Forty healthy men were fed diets providing 40% of energy from fat and a minimum of 25 mg vitamin E for 28 wk. During the first 10 wk diets were supplemented with placebo, 15 g mixed fat/d. During the second 10 wk placebo was replaced by 15 g fish-oil concentrate/d. During the last 8 wk 200 mg vitamin E/d was added to fish oil. Compared with placebo, fish-oil feeding significantly increased plasma glucose and decreased triacylglycerol, insulin, glucagon, growth hormone, and somatomedin C. The changes in plasma cholesterol, cortisol, and dehydroepiandrosterone sulphate (DHEA-S) were not significant. Fish oil plus vitamin E further decreased insulin, growth hormone, and DHEA-S and reversed the effect of fish-oil on somatomedin C. The changes in glucose, glucagon, growth hormone, and cortisol were not significant. Thus, changes in plasma glucose and lipids caused by dietary fish oil alone and with fish oil plus vitamin E appear to be due to alterations in hormones involved in carbohydrate and lipid metabolism.

PMID: 1832814 [PubMed - indexed for MEDLINE]