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Lipoic Select - Emphasizing the Fact that Lipoic Acid is Still Important When Supplementing Chronically Ill Patients

07/01/2016 - Product Newsletter #292

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An interesting aspect of clinical nutrition practice is that it is subject, like so many other endeavors in our society, to the sometimes unpredictable whims of trends and fashions.  In particular, due to our tendency to be fascinated with newness and complexity, sometimes we may under appreciate their subtle yet powerful impact on clinical outcome - due to the simplicity of many of the supplemental options that have been available to us for many years.  Because a central tenet of Moss Nutrition for years has been "back to basics", the thought recently occurred to me that we may have been under appreciating the value of lipoic acid when formulating nutritional protocols for chronically ailing patients.  Therefore, in this newsletter I would like to highlight published research on the various ways lipoic acid can impact human health with the hope you will make a simple product like Lipoic Select a more frequent consideration for patient supplementation.

HISTORY AND BASIC CHEMISTRY OF LIPOIC ACID

The paper "Alpha-lipoic acid as a pleiotropic compound with potential therapeutic use of diabetes and other chronic diseases" by Gomes and Negrato (Gomes MB & Negrato CA.  Diabetology & Metabolic Syndrome, Vol. 6, 2014) begins with some interesting history:

"Alpha-lipoic acid (ALA) was discovered in 1937 by Snell but only in 1951 it was isolated by Reed.  The first clinical use of ALA has

been described in Germany in 1959 for the treatment of acute poisoning with amanita phalloides commonly known as death cap (from mushrooms) a deadly poison widely distributed in Europe."

The authors next discuss the many important ways ALA impacts human biochemistry and physiology:

"Nowadays it is believed that ALA or its reduced form, dihydrolipoic acid (DHLA) have many biochemical functions acting as biological antioxidants, as metal chelators, reducing the oxidized forms of other antioxidant agents such as vitamin C and E and glutathione (GSH), and modulating the signaling transduction of several pathways, like insulin and nuclear factor kappa B (NFkB).  ALA has also been shown to improve endothelial dysfunction and to reduce oxidative stress post exercise training; it also protects against the development of atherosclerosis and inhibits the progression of an already established atherosclerosis plaque."

Of course, not to be overlooked is the fact that ALA is an important sulfur-based compound:

"As a sulfur containing substance, ALA is considered a thiol compound."

In turn, as you might expect, ALA is an important factor in glutathione metabolism.  More on that later.

It should also be noted that, while ALA is found in the diet, the body can also manufacture it:

"ALA is commonly found in dietary components such as vegetables (spinach, broccoli, tomato) and meats, mainly viscera and also in many dietary supplements.  ALA can be also synthesized through enzymatic reactions in plants and animals' mitochondria from octanoic acid and cysteine (as a sulfur donor)."

Another important point to note is that ALA actually consists of two isomers, the R and S forms:

"ALA exists in two enantiomeric (optical isomers) forms, R and S..."

The "R" form is generally considered the only active form in human physiology:

"Some experimental studies have shown that R-ALA has greater biopotency in several metabolic pathways compared to S-ALA."

What can be stated about ALA bioavailability from both supplements and food?  Gomes and Negrato point out:

"The absorption and bioavailability of ALA have been studied mainly from dietary supplements where ALA exists as an admixture of R-ALA and S-ALA.  In general, the absolute bioavailability of both enantiomers is not greater than 40% which decreases with food intake."

With the above in mind, it is extremely important to ingest ALA on an empty stomach:

"...ALA must be taken 30 min before meals."

After absorption the metabolic fate of ALA is the following:

"After oral intake, ALA is absorbed by the gastrointestinal tract and is transported to different organs such as brain because it has the potential of freely crossing the blood-brain barrier.  Independently of the original sources (diet or nutritional supplements) ALA is reduced to dihydrolipoic acid (DHLA) and is metabolized in the liver in different metabolites like bisnorlipoate and tetranorlipoate and has renal excretion."

SOME KEY CLINICAL PROPERTIES OF LIPOIC ACID

Antioxidant properties

As many of you are probably aware, ALA has important antioxidant functions:

"ALA and DHLA have some important advantages over other antioxidant agents such as vitamin E and C, because they have amphiphilic properties that confer their antioxidant actions in the membrane as well as in the cytosol."

In simpler terms, ALA and DHLA can function as an antioxidant in both fat soluble and water soluble environments.  In contrast, vitamin C tends to function only in water soluble environments and vitamin E only in fat soluble environments.

What else can be stated about the antioxidant properties of ALA?  The authors state:

ALA/DHLA can also regenerate other antioxidant substances such as vitamins C and vitamin E and the ratio of reduced/oxidized glutathione (GSH/GSSG)."

In addition, consider the following about the relationship between ALA/DHLA and glutathione:

"Glutathione is a sulfur tripeptide containing glutamate, cysteine and glycine.  Its biosynthesis depends on substrate availability (cysteine), which is enhanced by ALA/DHLA which converts cysteine into cysteine and also through gene expression."

CLINICAL ENTITIES IMPACTED UPON BY ALA

The remainder of the Gomes and Negrato paper discuss specific clinical entities impacted upon ALA/DHLA.  Listed below are some of the most important:

  • Metal chelation - "ALA/DHLA are considered as chelator compounds because they are able to chelate divalent and transient metal ions both in vivo and in vitro but by different mechanisms of action.  ALA chelates mostly Mn2+, Cu2+, Pb2+ and Zn2+.  In addition to the previously mentioned ions, DHLA is also able to chelate Hg2+ and Fe3+."  Before leaving this section, many of you may be aware of some controversy about ALA as a mercury chelator.  More on that later.
  • Insulin activity - "ALA has many actions in the insulin metabolic pathways, glucose uptake and glycogen synthesis with some differences between both isomers."
  • Alzheimer's Disease
  • Obesity
  • Nonalcoholic fatty liver disease
  • Burning mouth syndrome
  • Cardiovascular disease
  • Endothelial function
  • Cancer
  • Diabetic retinopathy
  • Diabetic nephropathy
  • Diabetic wound healing
  • Diabetic cardiovascular neuropathy

To conclude their paper, Gomes and Negreto present the following thought as to the clinical potential of lipoic acid:

"Currently, there are compelling evidences linking oxidative damage to the majority of chronic diseases with increasing prevalence worldwide such as obesity, diabetes mellitus, cardiovascular disease and Alzheimer's disease.  Considering the pleiotropic action of ALA upon different pathways associated with the above mentioned diseases, its use as a potential therapeutic agent seems promising."

CONTROVERSY: CAN ALA HAVE A COUNTERPRODUCTIVE EFFECT IN EFFORTS TO CHELATE MERCURY?

As was mentioned in the Gomes and Negrato paper above, ALA can be a valuable clinical tool in relation to our efforts to deal with mercury toxicity in our patients.  However, some have suggested that ALA administration may have the exact opposite effect of actually increasing mercury toxicity, particularly in the brain.  This controversy was addressed by Rooney in his paper "The role of thiols, dithiols, nutritional factors and interacting ligands in the toxicology of mercury" (Rooney JPK.  Toxicology, Vol. 234, pp. 145-156, 2007). 

As you will see from the quotes below, these conflicting findings can easily be explained by one of the most often ignored properties of human physiology and biochemistry in relation to the introduction of any substance into the body - DOSE MATTERS!!

Rooney states:

"ALA has been shown to be protective against the effects of acute mercury poisoning in several mammalian species when administered simultaneously or shortly after mercury exposure, provided a correct dosing of ALA was used (inappropriate doses were seen to increase toxicity)."

In addition:

"Whilst it would appear that ALA may have potential as a mercury chelator, it is also clear from the work of Donatelli and Grunert that the effect of ALA on mercury toxicity is dependent on dosage size and on the spacing of the dosages in time."

I realize that there is a popular assumption that nutritional supplements, because they are "natural," are "idiot-proof" and can be given at any dose under any circumstance with no risk whatsoever.  In addition, I also realize that there is now a corollary to this assumption that, when any substance is proven to not to be "idiot-proof" it should be completely eliminated from our therapeutic repertoire.  To me, this is indeed unfortunate.  I would rather view substances such as ALA using a basis of good science rather than popular assumptions.  What does good science say?  Substances such as ALA are valuable therapeutic tools that present virtually no risk when employed by knowledgeable health care professionals who understand that the potential value:potential risk ratio weighs very high towards potential value when used correctly at optimal doses on patients who demonstrate genuine need.  This is one of the main reasons that we strictly limit sales of all Moss Nutrition products to health care professionals and their patients.

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