L-Arginine Cream May Improve Blood Flow, Temperature in the Feet of Diabetics


Laurie Barclay, MD


Jan. 9, 2004 — Topical L-arginine cream improves blood flow and temperature in the feet of diabetics, according to the results of a preliminary trial published as a letter in the January issue of Diabetes Care.

"This pilot study showed that arginine does increase blood flow, but it is not yet clear if this translates into fewer foot ulcers or better healing of ulcers," American Diabetes Association Vice President Robert Rizza, MD, told Medscape. He is a professor of medicine in the division of endocrinology and diabetes at the Mayo Clinic in Rochester, Minnesota, and was not involved in this study.

L-arginine, an amino acid classified as a dietary supplement, is the biochemical precursor of nitric oxide, which controls local blood flow by relaxing endothelial smooth muscle. In diabetes, L-arginine levels are reduced while levels of asymmetric dimethylarginine, an inhibitor of the enzyme that converts L-arginine to nitric oxide, are elevated. Transdermal delivery of exogenous L-arginine via patented technology is said to restore blood flow by reversing these biochemical defects.

In this double-blind, vehicle-controlled, crossover-design pilot with washout periods of one week, 16 subjects with diabetes and impaired foot circulation were enrolled and 13 completed the study. With L-arginine cream, average Doppler flow increased 33% at the metatarsal and 35% at the Achilles tendon, and average temperature increased 5 degrees at the metatarsal and 8 degrees at the great toe.

"That is a huge amount," study author Eric T. Fossel, PhD, told Medscape. "It is true that this was a small study, but these are very convincing statistics." Dr. Fossel is president of Strategic Science and Technologies in Wellesley, Massachusetts, which holds the patent for L-arginine cream.

Because the effect of L-arginine persisted throughout the washout period, Dr. Fossel altered the analysis to determine the effect from cumulative exposure to L-arginine throughout the study. This eliminated the possibility of comparing active cream with placebo.

Dr. Rizza called these findings "intriguing but preliminary" and recommended additional research to determine if the cream has any clinical benefit in preventing or reducing amputations or other foot complications.

"We need better treatments, but there are many things that diabetics can do to reduce their risks," he said, urging daily foot inspection, better glucose control, exercise, quitting smoking, and protecting the feet with well-fitting shoes.

(Additional reporting by Salynn Boyles.)

Diabetes Care. 2004;27:284-285

Further advances in topical applications for the A2 topographical areas?

I think blood flow in the trouble areas is a largely underappreciated factor (re-esterfication being a proiment issue).

lyle wrote an interesting chapter about this in the UD 2.0.
that chapter made me understand why I lost a lot of lower BF using T3.

lile roolz!!!!!!

lol lol

Lyle

Lyle, you are aware there's an edit feature on the posts, correct?

Lyle,
I think people have brains, they just don't stimulate them.  They let them atrophy.

A shame.

My way is more fun.

Lyle

Sing it with me, guys
Ninja love...

a. I remain unconvinced that topically applied stuff will even hit the microcirculation of adipose tissue (and Par's refs don't provide a very good argument that it will). The vasculature of the skin is just too well developed.

Aren't you forgetting DMSO?

a. I remain unconvinced that topically applied stuff will even hit the microcirculation of adipose tissue (and Par's refs don't provide a very good argument that it will). The vasculature of the skin is just too well developed

Where's Par?....fight fight.....

Perhaps that is the reason I didn't have much luck with lipoderm and L-ultra beyond what a regular diet would have provided.

Where's Par?....fight fight.....

Perhaps that is the reason I didn't have much luck with lipoderm and L-ultra beyond what a regular diet would have provided.

What, specifically, is it about the studies, or conclusions drawn from them, that you disagree with?? They showed a much higher ratio of actives in deep, local tissues compared to tissues associated with systemic delivery with the local carrier vs. oral and another transdermal formulation.

"I have several creams in my country that are supposed to reduce BF.
the main ingredients are usually t3, t4, or iodium.
they seem to work, maybe reducing water retention in the treated areas"

Are you referring to Nemectron, Thiomucase, and Alec Eden-Slendertone by any chance?

"I should note that such products should still have *some* effect as a conseqeuence of evntually hitting central circulation and affecting things that way. I'm simply not convinced that they are getting where we want them (directly on the fat cell) b/c of the massive vascularization of the dermis."

My understanding is that the connective-tissue structure/fibers located between the dermis and subcutaneous "tissue" (aka. the corium) -contains different amounts of "polygonal" fat cells along the border "zone" of the corium. If this is accurate, then the elastic fiber cells of the corium would likely allow fat cells to migrate to the the dermis. Subcutaneous fat cell chambers could hypertrophy and cause distended lymphatic vessels.

I think that this is probably an area that can be directly targeted by the actives since penetration of the dermis would be all that would be required for adipose tissue to be "activated"...

From what I gathered from the abstracts, they showed that the compounds penetrated the outer dermis.

BFD.

None of the ones you sent me said anything about adipose tissue, only that it got through the outer layer of the dermis better than the other compounds. You're making the kinds of bullshit extrapolations that are all too common in this field.

And considering the extreme vascularity of the skin, well....I remain unconvinced that you're getting significant amounts to the adipose tissue systemically with this mode of delivery. It's possible mind you but I do'nt think the studies you are referencing support that conclusion at all.

Maybe if you use an insulin needle.

Lyle

My understanding is that the connective-tissue structure/fibers located between the dermis and subcutaneous "tissue" (aka. the corium) -contains different amounts of "polygonal" fat cells along the border "zone" of the corium. If this is accurate, then the elastic fiber cells of the corium would likely allow fat cells to migrate to the the dermis. Subcutaneous fat cell chambers could hypertrophy and cause distended lymphatic vessels.

I think that this is probably an area that can be directly targeted by the actives since penetration of the dermis would be all that would be required for adipose tissue to be "activated"...

And that's still not going to affect deep SAT.

For fuck's sake, Lyle, you only read the abstracts, and you are not just drawing conclusions, but talking shit ("Bullshit extrapolations"), too...??

Read the full papers -- they looked at concentrations in not just skin, but muscle, joint capsules, and organs, such as brain, liver, etc., in oral vs. special transdermal vs. another transdermal formulation.

The formula we based our design on was greatly superior for what we want, obviously.

To summarize the best study:

The first study (19b) involved the NSAID indomethacin as the drug to be delivered. The drug was given orally (O) , topically without the "special delivery solvent" (WO), and with the "special delivery solvent" (W). The topicals were applied to the shoulder. For the first two hours after administration, concentrations of the drug in the deltoid (which is obviously even deeper than adipose tissue) were 5 times higher in W than in either O or WO. After 4 hours, it was 3 times as high, and by 8 hours it was still twice as high. Obviously, the formulation containing the "special delivery solvent" was vastly superior at delivering the drug to the target tissue. But what about delivery to unwanted tissues? If it was just a case of the "special delivery solvent" allowing more drug to cross the skin, this would not be a big deal -- we could just use more. What we also need is for a minimal amount of the drug to be delivered systemically, and once again, the "special delivery solvent" was shown to be superior. Maximal blood levels of all three compounds occurred at the 2 hour mark. W displayed levels about 1/3 that of O and 1/2 that of WO.

If the significance of this is not clear, it basically means that localized delivery (what we want) per unit systemic delivery (what we don't want) for W was 15 times that of O and 10 times that of WO -- and this was to the muscle. Considering the adipose tissue is closer to the skin (which had levels 10 times as high as the muscle) and that the joint capsule (which is below the muscle) had levels 1/3 that of the muscle while with WO there were equal levels at the muscle and joint, the ratio of delivery to adipose tissue vs. systemic delivery for W is likely significantly higher.

I have a friend whose girlfriend was trained and measured by Charles Polliquin who lost 11mm of thigh skinfolds, with zero loss anywhere else, in a few weeks on LipoDerm. And, of course, there are countless bits of similar, if less drastic, bits of feedback over the last 3 years.

Since I was "there" I will back Par on this one.
During brief period, Lipoderm worked wonders on the hamstring area.
A slightly less reduction was seen in the thigh. Note: the caloric deficit wasn't huge and these results were within a very small time frame. Ten days or something. (And this was without a washout period. Remember we were using the
original formula=0 diuretic). There was a trend towards thigh reduction- it is my "guess" that was next to go. Upper body skinfolds lost next to nothing. Or nothing worth talking about. That was "dramatic" part if you get excited about such things...

Unfortunately, "the girlfriend" fell a back into her ADHD ways and abandoned further experimentation. 10 days is a long time

Oh Yeah and zero cardio of course.

The dosing with LipoDerm is quite high (200mg per day) -- and, we suggest lower dosing with less fat, higher dosing with more.

Plus, even if you reach only say the outer 1/3 of a fat ass, it is still going to help get rid of that outer third, which will then bring the other 2/3 closer to the surface, and so on.

I have a friend whose girlfriend was trained and measured by Charles Polliquin who lost 11mm of thigh skinfolds, with zero loss anywhere else, in a few weeks on LipoDerm. And, of course, there are countless bits of similar, if less drastic, bits of feedback over the last 3 years.

Given that we have had almost zero advertising, attract customers with science (so, they tend to be smarter than the average) and word of mouth, do you guys really believe that we have built a large customer base and a huge amount of overwhelmingly positive feedback and very little negative just on placebo effect and confounding variables??

You miss my point. I am not defying that your topical cream does not work, or does work. I am merely pointing out the inefficiencies. I've had my own 'recipe' concocted long before any of you guys started on this. The real test will be what I had proposed a few years ago, but I don't have enough raw materials to support such an experiment: treat one thigh and not the other. The untreated leg serves as the treated leg's control.

Microdialysis would be nice, but again, that's a bit out of my capabilities.

Well, sure it would have inefficiencies -- and, I don't even think you mentioned the stratum corneum.

But, even with injections, you are still going to have metabolism, and you are still going to have diffussion into and uptake by the vasculature.

And, many do not like the idea of sticking thelmselves all over with little needles.

Then you should state your point more clearly.

You could try improving your reading comprehension.

QUOTE 

I think blood flow in the trouble areas is a largely underappreciated factor (re-esterfication being a proiment issue).



not by those of us with a brain.

...Furthermore CGRP is one of the most potent—if not the most potent –vasodilator naturally produced by the human body. So, it should substantially increase blood flow to the area, allowing for removal of the fatty acids that are released by Lipoderm’s lipolytic ingredients....

that those who understand what is going on