Wasting Disease and Atrophy

Dear Jill: There are many causes of muscle wasting disease, but I will briefly a couple of causes. Some people who use statin drugs (e.g. lovastatin) to lower cholesterol as being the cause by inducing expression atrogin-1 which causes muscle wasting as a clue to a possible remedy. The key is to find a natural remedy against overexpression of atrogin-1 without the need for genetic engineering. One clue is the use of curcumin, by taking perhaps three times a day (one or two teaspoon), this might suppress atrogin-1 muscle wasting disease. See research on both research regarding lavostatin and curcumin is the possible remedy below, even if statins were not taken but it might be some environmental or dietary trigger to cause muscle wasting disease.

The lack of Insulin Growth Factor IGF-1 might also be possible from other factors which suppresses this and finding certain supplements to enhance IGF-1 may help the building of muscles, and there are Growth Hormones which does that. Or the use of certain secretagogues that may also help naturally increase growth hormones such as taking 300 mg of niacinamide, 4000 milligrams glycine, 4000 grams of l-glutamine once before bedtime is just one example. Although some cases it may involved lack of mineral deficiency, and this can be somewhat roughly determine what is causing the problem through hair mineral analysis. Selenium is just one of them that maybe needed. My own experience of an aging grandmother of 80 years old due to aging resulting in muscle wasting I found the muscles to increase enormously to that of a young person's muscles just through the use of vitamin D3 (preferably D4), taking at about 25,000 i.u. per day for about two months, with some magnesium citrate supplements to keep the magnesium/calcium to be in balance. The muscle should first notice such growth after about 3 weeks. However, weakness of the legs or muscle degeneration can even be generated if that person never eats fresh fruits rich in vitamin C. The vitamin C I prefer is sodium ascorbate vitamin C 500-1500 mg. and some ester C vitamin C, preferably the magenesium ones, if they have one, perhaps just 250 mg for that. Some vitamin B complex (the B50 kind) and vitamin E 400 i.u.) may also be helpful in reducing weakness which can result in some atrophy from the weakness. Body builder's nutrition can also help in some cases of atrophy from such supplements as glutamine, creatinine, human growth hormone, testosterone, etc. which will be more than enough to try on.

However, I would prefer to deal with the neural disorders as one of the possible cause for at least a couple of weeks or a month (if there's enough time) in detoxification from free heavy metals as neural damage may also lead to long term atrophy. If the body has heavy metal in presence of certain hormonal like supplements may lead to excess free radicals which might not be that lasting. Therefore, I prefer to use glutathione supplements such taken three times a day, usually 500 mg is the common dose. To reduce heavy metals, chlorella supplements 500 mg taken for about two weeks. During this time the vitamin D3 (preferably D4) and vitamin C sodium ascorbate, some vitamin E 200 i.u, and twice or three times a week B50 vitamin B complex and magnesium citrate 500 mg can be taken, as these in general won't increase free radicals. Alkalization may also allow the body to heal, such as taking 2 tablespoon of lime juice or lemon plus 1/2 teaspoon of baking soda in 1/2 glass of water (at least) taken twice a day. For some reason or another, body seems to build better when it is in more alkaline state and tends to digest itself or atrophy whenever the body is in acidosis phase. Certain neuroprotective supplements such as 1 tablespoon a day of granulated lecithin (insulates myelin and protect the nerve conduction) plus perhaps a nutrient dense 2-4 tablespoon a day of chinese wolfberries (in form of red raisin, or other forms would be fine). The chinese wolfberries are neuroprotective. Than after about a 3 weeks or a month, I might consider taking those body builder supplements. Of course curcumin can be taken any time too. No statin drugs and granulated lecithin and chinese wolfberries for example can easily reduce triglycerides and cholesterol anyway.

Again, some hair mineral analysis here may be helpful in identifying the problem. Sometimes unexpected happens where high mercury or other heavy metals might even lead to atrophy or perhaps it was a deficiency can further provide some clues.

Ted

J Clin Invest. 2007 Nov 8; [Epub ahead of print] Links The muscle-specific ubiquitin ligase atrogin-1/MAFbx mediates statin-induced muscle toxicity. Hanai JI, Cao P, Tanksale P, Imamura S, Koshimizu E, Zhao J, Kishi S, Yamashita M, Phillips PS, Sukhatme VP, Lecker SH.

Renal Division and Division of Interdisciplinary Medicine and Biotechnology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA. National Research Institute of Fisheries Science, Yokohama, Japan. Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts, USA. Tokyo University of Marine Science and Technology, Tokyo, Japan. Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, USA. Scripps Mercy Hospital, San Diego, California, USA.

Statins inhibit HMG-CoA reductase, a key enzyme in cholesterol synthesis, and are widely used to treat hypercholesterolemia. These drugs can lead to a number of side effects in muscle, including muscle fiber breakdown; however, the mechanisms of muscle injury by statins are poorly understood. We report that lovastatin induced the expression of atrogin-1, a key gene involved in skeletal muscle atrophy, in humans with statin myopathy, in zebrafish embryos, and in vitro in murine skeletal muscle cells. In cultured mouse myotubes, atrogin-1 induction following lovastatin treatment was accompanied by distinct morphological changes, largely absent in atrogin-1 null cells. In zebrafish embryos, lovastatin promoted muscle fiber damage, an effect that was closely mimicked by knockdown of zebrafish HMG-CoA reductase. Moreover, atrogin-1 knockdown in zebrafish embryos prevented lovastatin-induced muscle injury. Finally, overexpression of PGC-1alpha, a transcriptional coactivator that induces mitochondrial biogenesis and protects against the development of muscle atrophy, dramatically prevented lovastatin-induced muscle damage and abrogated atrogin-1 induction both in fish and in cultured mouse myotubes. Collectively, our human, animal, and in vitro findings shed light on the molecular mechanism of statin-induced myopathy and suggest that atrogin-1 may be a critical mediator of the muscle damage induced by statins.

J Clin Invest. 2007 Nov 8; [Epub ahead of print] Links The muscle-specific ubiquitin ligase atrogin-1/MAFbx mediates statin-induced muscle toxicity. Hanai JI, Cao P, Tanksale P, Imamura S, Koshimizu E, Zhao J, Kishi S, Yamashita M, Phillips PS, Sukhatme VP, Lecker SH.

Renal Division and Division of Interdisciplinary Medicine and Biotechnology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA. National Research Institute of Fisheries Science, Yokohama, Japan. Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts, USA. Tokyo University of Marine Science and Technology, Tokyo, Japan. Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, USA. Scripps Mercy Hospital, San Diego, California, USA.

Statins inhibit HMG-CoA reductase, a key enzyme in cholesterol synthesis, and are widely used to treat hypercholesterolemia. These drugs can lead to a number of side effects in muscle, including muscle fiber breakdown; however, the mechanisms of muscle injury by statins are poorly understood. We report that lovastatin induced the expression of atrogin-1, a key gene involved in skeletal muscle atrophy, in humans with statin myopathy, in zebrafish embryos, and in vitro in murine skeletal muscle cells. In cultured mouse myotubes, atrogin-1 induction following lovastatin treatment was accompanied by distinct morphological changes, largely absent in atrogin-1 null cells. In zebrafish embryos, lovastatin promoted muscle fiber damage, an effect that was closely mimicked by knockdown of zebrafish HMG-CoA reductase. Moreover, atrogin-1 knockdown in zebrafish embryos prevented lovastatin-induced muscle injury. Finally, overexpression of PGC-1alpha, a transcriptional coactivator that induces mitochondrial biogenesis and protects against the development of muscle atrophy, dramatically prevented lovastatin-induced muscle damage and abrogated atrogin-1 induction both in fish and in cultured mouse myotubes. Collectively, our human, animal, and in vitro findings shed light on the molecular mechanism of statin-induced myopathy and suggest that atrogin-1 may be a critical mediator of the muscle damage induced by statins.

Am J Physiol Endocrinol Metab. 2004 Oct;287(4):E591-601. Epub 2004 Apr 20. Links IGF-I stimulates muscle growth by suppressing protein breakdown and expression of atrophy-related ubiquitin ligases, atrogin-1 and MuRF1. Sacheck JM, Ohtsuka A, McLary SC, Goldberg AL. Collaborators (1)

Department of Cell Biology, Harvard Medical School, 240 Longwood Ave., Boston, MA 02115, USA.

Muscle atrophy results primarily from accelerated protein degradation and is associated with increased expression of two muscle-specific ubiquitin ligases (E3s): atrogin-1 and muscle ring finger 1 (MuRF1). Glucocorticoids are essential for many types of muscle atrophy, and their effects are opposite to those of insulin-like growth factor I (IGF-I) and insulin, which promote growth. In myotubes, dexamethasone (Dex) inhibited growth and enhanced breakdown of long-lived cell proteins, especially myofibrillar proteins (as measured by 3-methylhistidine release), while also increasing atrogin-1 and MuRF1 mRNA. Conversely, IGF-I suppressed protein degradation and prevented the Dex-induced increase in proteolysis. IGF-I rapidly reduced atrogin-1 expression within 1 h by blocking mRNA synthesis without affecting mRNA degradation, whereas IGF-I decreased MuRF1 mRNA slowly. IGF-I and insulin also blocked Dex induction of these E3s and several other atrophy-related genes ("atrogenes"). Changes in overall proteolysis with Dex and IGF-I correlated tightly with changes in atrogin-1 mRNA content, but not with changes in MuRF1 mRNA. IGF-I activates the phosphatidylinositol 3-kinase (PI3K)-Akt pathway, and inhibition of this pathway [but not the calcineurin-nuclear factor of activated T cell (NFAT) or the MEK-ERK pathway] increased proteolysis and atrogin-1 mRNA expression. Thus an important component of growth stimulation by IGF-I, through the PI3K-Akt pathway, is its ability to rapidly suppress transcription of the atrophy-related E3 atrogin-1 and other atrogenes and degradation of myofibrillar proteins.