[suzierose]

Stopping Muscle Wasting on Dexamethasone

by suzierose on Mon Oct 24, 2011 9:12 pm

Can multiple myeloma patients take glutamine, arginine and HMB to prevent muscle wasting while on dexamethasone?



Glutamine-
Muscle cell concentrations of glutamine are far higher than blood levels. Plasma and intramuscular glutamine concentrations drop during metabolic stress such as surgery, burns, or trauma (9). Glutamine also increases heat-shock proteins which increase muscle hypertrophy (10, 11). Heat-shock proteins are ‘cellular chaperones’ involved in the management of stress-induced protein cell destruction. Glutamine depletion results in diminished synthesis of heat-shock proteins.
Recently, glutamine has been shown to increase heat-shock protein approximately fourfold in critical illness (12). Glutamine can also increase tissue glutathione levels and enhance antioxidant capacity. The use of glutamine seems to be especially warranted during dieting when caloric restriction, exercise frequency, and exercise intensity are at their highest.

Arginine-

Dietary supplementation with arginine has also been shown to safely induce positive nitrogen balance in humans possibly by increasing muscle protein synthesis and inhibiting muscle proteasome (enzymes that breakdown muscle) activity (38). The most important pathway of arginine metabolism appears to be its conversion to orthinine in the liver, which is a precursor for protein synthesis. Arginine supplementation, usually up to 20 g/d, has been reported to reduce weight loss and nitrogen loss and improve nitrogen retention and wound healing.
The mechanism for this action is unclear. One mechanism may be stimulation of the release of GH release. Another mechanism may be thru stimulation of nitric oxide production. As NO is directly involved in many physiological mechanisms relevant to hormone release, and muscle regeneration. For example, the enhanced muscle regeneration effects of L-arginine appears to be dependent on the NO pathway, as supplemental dietary arginine enhances muscle regeneration in normal but not those deficient in NO (25).

Beta-hydroxy beta-methylbutyrate (HMB) -

is a metabolite of the branched-chain amino acid leucine. HMB is metabolite of the amino acid leucine, leucine alone can stimulate protein synthesis, inhibit protein breakdown, and reduce activation of UPP (46).

[Dr. Peter Voorhees]

Re: Stopping Muscle Wasting on Dexamethasone

by Dr. Peter Voorhees on Tue Oct 25, 2011 5:20 am

Dear Suzierose,

The cautious answer is that we do not know. I do not see any obvious reasons why this could not be done with dexamethasone. However, there are at least some theoretical reasons why this may not be desirable with a proteasome inhibitor like Velcade (bortezomib). There are laboratory data that would suggest that proteasome inhibitors work against myeloma cells by inducing oxidative stress. As such, something that can protect against oxidative damage could diminish the myeloma response to the Velcade. I should stress that this is not well studied and just a theoretical concern. Additionally, laboratory data would also suggest that induction of a heat shock response can decrease the effectiveness of proteasome inhibitors. This is the basis for on-going clinical trials evaluating the use of heat shock protein inhibitors in combination with Velcade-based therapy.

We definitely need more clinical data to determine the effectiveness of supplements in reducing chemotherapy-related side effects and whether or not they decrease (or increase) the effectiveness of myeloma therapy.

One thing that we can all agree on is that steroids can have serious side effects. As such, we need to use them very carefully.

Good luck!

Pete V.