Iron depletion more effective than diet in reducing insulin levels

According to this study: one group was given phlebotomy (to reduce iron), and another group was given nutritional counseling, both with the goal of reducing insulin levels. The group that did the iron depletion had a much greater improvement to insulin resistance than the diet group. I think what this means for us is that we need to not worry so much about sugars and grains, we need to worry about red meat and other foods with high iron content if we want to keep our hair.

http://www.ncbi.nlm.nih.gov/pubmed/17391316

OBJECTIVES: Hyperferritinemia is frequently observed in nonalcoholic fatty liver disease (NAFLD), the hepatic manifestation of the metabolic syndrome characterized by hepatic insulin resistance and considered high cardiovascular risk. Iron depletion by phlebotomy has been reported to decrease insulin resistance in NAFLD in small, uncontrolled studies. Aims of this study were to define the relationship between ferritin and iron stores in patients with NAFLD, the effect of iron depletion on insulin resistance, and whether basal ferritin levels influence treatment outcome. METHODS: Subjects were included if ferritin and/or ALT were persistently elevated after 4 months of standard therapy. Sixty-four phlebotomized subjects were matched 1:1 for age, sex, ferritin, obesity, and ALT levels with patients who underwent lifestyle modifications only. Insulin resistance was evaluated by insulin levels, determined by RIA and the HOMA-R index, at baseline and after 8 months. RESULTS: Baseline ferritin levels were associated with body iron stores (P<0.0001). Iron depletion produced a significantly larger decrease in insulin resistance (P=0.0016 for insulin, P=0.0042 for HOMA-R) compared with nutritional counseling alone, independent of changes in BMI, baseline HOMA-R, and the presence of the metabolic syndrome. Iron depletion was more effective in reducing HOMA-R in patients in the top two tertiles of ferritin concentrations (P<0.05 vs controls), and in carriers of the mutations in the HFE gene of hereditary hemochromatosis (P<0.05 vs noncarriers). CONCLUSIONS: Given that phlebotomy reduces insulin resistance, which is associated with liver tissue damage, future studies should evaluate the effect of iron depletion on liver histology and cardiovascular end points.

Espio - Great info here. I won't give up red meat, but I will start increasing my use of IP6 (Insositol hexaphosphate).

This is amazing info and timely too since I just recently started using IP6 myself. On iherb and elsewhere there are several reviews mentioning IP6's effectiveness against most forms of cancer.
IH - since you have been using IP6 for a while now, how do you use it that you believe offers the best results? The main issues for me are that it apparently has to be taken about 3 hours since one's last meal and 30-60 mins before the next one. Also the fact that one hour after taking the IP6 I worry that whatever supplements I take with that meal might get chelated out just like the iron.

zerx - The only time I take IP6 is at nighttime, well after any meals and/or supplements.

One of the reasons I want to keep eating beef (besides the taste) is to get the benefits of carnosine in the diet.

J Agric Food Chem. 2005 Jun 15;53(12):4736-9.
http://www.ncbi.nlm.nih.gov/pubmed/15941308

From my experience, taking IP6 alone does not do much for lowering iron. I haven't seen any studies that show that it is effective in reducing iron, have you? I asked my Dr. at the university and he never heard of IP6, the only way he knew of lowering iron was by donating blood.

I had taken over 200 capsuls of 500 mg each of Jarrow's IP6 in the two months before I took a ferritin blood test, and it was still high (160). Dr. Mercola's website advises getting your ferritin under 100. So that leaves two possibilities, either IP6 does not do much to lower iron, or my iron levels must of had a high iron overload before I started taking the IP6. I don't believe it could have been the latter because if I had an iron overload I would of seen poor liver functioning in previous blood tests due to iron overload.

Espio - I took a long look at this and I can't find any supporting evidence that IP6 works to remove iron. The only thing I could find is that it improves the oxygenation of hemoglobin. Additionally, IP6 is very promising in studies as an anti-cancer agent. Perhaps Bill Sardi, the most well known supporter of IP6 was right about IP6 and cancer, but wrong on the iron chelating factor.

Here is more evidence of protection from IP6: Perhaps the "iron chelating" isn't the key, maybe it is protection from high iron instead.

Toxicology. 2008 Mar 12;245(1-2):101-8. Epub 2007 Dec 27.
Neuroprotective effect of the natural iron chelator, phytic acid in a cell culture model of Parkinson's disease.
Xu Q, Kanthasamy AG, Reddy MB.

Department of Biomedical Sciences, Iowa State University, Ames, IA, United States.

Disrupted iron metabolism and excess iron accumulation has been reported in the brains of Parkinson's disease (PD) patients. Because excessive iron can induce oxidative stress subsequently causing degradation of nigral dopaminergic neurons in PD, we determined the protective effect of a naturally occurring iron chelator, phytic acid (IP6), on 1-methyl-4-phenylpyridinium (MPP(+))-induced cell death in immortalized rat mesencephalic/dopaminergic cells. Cell death was induced with MPP(+) in normal and iron-excess conditions and cytotoxicity was measured by thiazolyl blue tetrazolium bromide (MTT assay) and trypan blue staining. Apoptotic cell death was also measured with caspase-3 activity, DNA fragmentation, and Hoechst nuclear staining. Compared to MPP(+) treatment, IP6 (30 micromol/L) increased cell viability by 19% (P<0.05) and decreased cell death by 22% (P<0.05). A threefold increase in caspase-3 activity (P<0.001) and a twofold increase in DNA fragmentation (P<0.05) with MPP(+) treatment was decreased by 55% (P<0.01) and 52% (P<0.05), respectively with IP6. Cell survival was increased by 18% (P<0.05) and 42% (P<0.001) with 30 and 100 micromol/L of IP6, respectively in iron-excess conditions. A 40% and 52% (P<0.001) protection was observed in caspase-3 activity with 30 and 100 micromol/L IP6, respectively in iron-excess condition. Similarly, a 45% reduction (P<0.001) in DNA fragmentation was found with 100 micromol/L IP6. In addition, Hoechst nuclear staining results confirmed the protective effect of IP6 against apoptosis. Similar protection was also observed with the differentiated cells. Collectively, our results demonstrate a significant neuroprotective effect of phytate in a cell culture model of PD.

Thats well and good IH but what what of all those reviews with people mentioning how their iron levels went down. I was really into IP6 for its iron chelating properties and I hope that is still true.

zerx - Me too, I hope it does work. One thing is for sure, it's definitely good against cancer and Candida, and increases oxygen in the blood, so that is all very positive. Also, it does protect against high iron damage. Hopefully one of us will find some supporting researching on its chelating activities.

CausticSymmetry wrote:Espio - Great info here. I won't give up red meat, but I will start increasing my use of IP6 (Insositol hexaphosphate).

Cross over to the veggie-side with me IH.

:p

http://jn.nutrition.org/cgi/content/abstract/128/11/1950

Phytic Acid Inhibits Free Radical Formation In Vitro but Does Not Affect Liver Oxidant or Antioxidant Status in Growing Rats

Manuscript received 8 April 1998. Initial reviews completed 21 May 1998. Revision accepted 30 June 1998.

Gerald Rimbach and Josef Pallauf
Institute of Animal Nutrition and Nutrition Physiology, Justus-Liebig-University, D-35390 Giessen, Germany

The objective of this study was to determine the effects of phytic acid on free radical generation in vitro and in growing rats. Electron spin resonance spectroscopy studies using 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) as a spin trap indicate a complete inhibition of hydroxyl radical formation via the iron-catalyzed Fenton reaction at molar phytic acid/iron ratios >5. However, phytic acid had no scavenging effect on superoxide radicals generated in the xanthine/xanthine oxidase reaction. For the in vivo study, male growing albino rats were fed purified diets based on casein, cornstarch and vitamin E-stripped corn oil differing in the concentration of iron (30 or 300 mg/kg), phytic acid (0 or 10 g/kg) and dl--tocopheryl acetate (0 or 50 mg/kg). At marginal dietary iron supply, phytic acid supplementation reduced apparent Fe absorption, thereby decreasing liver Fe concentration. Dietary iron and phytate had no effect on the level of hepatic -tocopherol, reduced glutathione, thiobarbituric acid-reactive substances and protein carbonyls. The concentration of thiobarbituric acid-reactive substances and protein carbonyls in the liver decreased as dietary vitamin E was increased from 0 to 50 mg/kg diet. The results obtained provide evidence for antioxidant properties of phytic acid under in vitro conditions. However, neither phytic acid nor iron had any significant effect on liver oxidant or antioxidant status in vivo in growing rats.

IH - probably a silly question but I couldnt find a clear answer on this. Would taking a humifulvate product, like say Swansons Metal Shield be helpful in reducing iron levels? I know iron isnt a true "heavy metal", but i wonder if this product would still be helpful in reducing it.

You probably know which one I am refering to since you have recommended it in the past, but here is the link to what Im talking about. Dr. Laszlo Meszaros' Metal Shield - http://www.swansonvitamins.com/SWU420/ItemDetail#

Anyone else take/know about this btw?

roject: JS - humifulvate does not to bind iron, but in fact actually supplies some iron. So unfortunately, it won't us any good with respect to iron.

However, any of us who are using Lipoic acid are getting protection from iron. Here is a good article on its role in inflammation and Atherosclerosis.

http://lpi.oregonstate.edu/ss03/lipoicacid.html

Thank you IH.. Thats good information. And great article btw. Its kind of amazing how helpful a supplement ALA is - on multiple levels even..

Project: JS - I totally agree. I first learned about Lipoic acid in '95 and at the time it was quite expensive. I remember seeing Jarrow having a 60 capsule count of 100 mg regular alpha lipoic acid for 30 bucks. These days one can buy 240 capsules of 100 mg ALA for 8 bucks.

Of course I take the N-Rala form. But in any form I think it's the most important antioxidant to take and a way to engender life extension and most diseases of oxidative stress.

On a side note, there is a new breakthrough in COPD (Chronic Obstructive Pulmonary Disease) that I should mention, because this is a disease where not even lipoic acid would make much of a dent in.

The breakthrough is using the ingredient sulphoraphane. This comes from the cruficerious vegetables like Broccoli, Cabbage, etc. The latest research shows this can actually reverse COPD, so if anyone knows of relatives with this problem, there is real hope here.

IH - hope for the future.. thats outstanding. I love how everytime I come on here Im finding out new good treatment options for serious diseases. Thank you.

CausticSymmetry wrote:
The breakthrough is using the ingredient sulphoraphane. This comes from the cruficerious vegetables like Broccoli, Cabbage, etc.

Yet another way to get your SGS:

http://www.brassicatea.com

IH Since you take IP6 only once a day, how many grams is your daily dose. Also, how long do you plan to take it for and do you plan to do it periodically.

zerx - I'm glad this thread was made because like most people, I just accepted that IP6 was an iron chelator. Turned out it only protects against iron damage but it does improve the transport of oxygen via hemoglobin.

Before this understanding, I was taking load of IP6 periodically (one per week), usually a few grams at per dose (3 to 4 capsules). But not I place most of the positive expectations on the lipoic acid, which helps deal with the iron the best.

So when my IP6 supply runs out (I will probably quit it all together). Lipoic acid has plenty of supporting research showing at least a partial chelating effect on iron, but more importantly good protection from iron.

In this latest study shows very potent protection from a combination of Lipoic Acid & Acetyl L-Carnitine.

Redox Rep. 2008;13(1):2-10.
Lipoic acid and acetyl-carnitine reverse iron-induced oxidative stress in human fibroblasts.
Lal A, Atamna W, Killilea DW, Suh JH, Ames BN.

Nutrition & Metabolism Center, Children's Hospital Oakland Research Institute, Oakland, California, USA. alal@mail.cho.org

Iron overload occurs frequently in thalassemia and other disorders that require regular blood transfusions. Excess iron is toxic owing to the generation of free radicals that lead to oxidation of biomolecules and tissue damage. In order to identify compounds that reduce oxidative injury from iron, we evaluated alpha-lipoic acid (LA), a multifunctional antioxidant, in iron-overloaded primary human fibroblasts (IMR-90). Oxidant stress was measured using dichlorodihydrofluorescein diacetate that is converted to the fluorescent dichlorofluorescein (DCF) upon oxidation. Exposure to ferric ammonium citrate (FAC) increased the iron-content of IMR-90 cells and caused a rise in oxidant appearance. The addition of LA improved the cellular redox status and attenuated the iron-mediated rise in oxidants in a dose-dependent manner. The R- and RS-enantiomers of LA demonstrated similar antioxidant activity. N-tert-butyl hydroxylamine (NtBHA) treated cells also exhibited a decrease in DCF fluorescence, but at a much higher concentration compared with LA. The combination acetyl-L-carnitine (ALCAR) and LA exhibited superior antioxidant effect at all dose levels. We conclude that LA is highly effective in reversing oxidative stress arising from iron overload and that its antioxidant efficacy is further enhanced in combination with ALCAR.

Hi! New to this forum and to doing something smart about my hairloss and overall health.

I have Thalessemia Minor (meaning no transfusions and generally not an issue). Is it safe for me follow IH's regimem and/or should I be altering it in some way to account for my condition.

Thanks.

MadGreek - From what I know, I do not believe there are any complications concerning Thalassemia minor and the regimen.