Alpha Lipoic Acid: The Wonder Supplement

By William Harryman (2003)

[This article originally appeared in Equilibrium, in the 21st Century Body column by
William Harryman.]

While Americans are wasting large sums of money on coral calcium (which is no better
than standard calcium), worthless ephedra-free diet pills, and so many other expensive
supplements that don't do what they promise, there is one supplement that does work and
gets very little attention: alpha lipoic acid (ALA). ALA is one of the most potent
antioxidants available. It increases insulin sensitivity, helps the body dispose of blood
sugar, eases the pain of neuropathy, protects against nerve cell death, and has other
benefits as well.

A Powerful Antioxidant

Doctor Lester Packer (UC Berkeley) has proposed four criteria for assessing the
effectiveness of antioxidants: specificity of free radicals they attack, metal chelating
ability (forms molecules with a metal ion), interaction with other antioxidants, and effects
on gene expression. Dr. Packer wrote a review article on ALA (Free Radical Biology &
Medicine) in which he stated that ALA approaches the ideal for an antioxidant.

As has been shown in a wide variety of studies over the past three decades, many of the
negative events associated with aging are the result of free radical damage at the DNA
level in our cells. Among the negative events are cancers (cell growth that is out of
control or highly abnormal) and arterial diseases (including strokes). In addition, there is
likely a connection between free radicals and neurodegenerative brain diseases, such as
Parkinson's disease and Huntington's disease. Antioxidants are so important to our health
because they neutralize free radicals in the body and prevent them from damaging cells.

ALA is both fat-soluble and water-soluble, unlike many other antioxidants that are one or
the other (vitamin E is only fat-soluble, vitamin C is only water-soluble). What this
means is that ALA has antioxidant effects both in cellular lipids (the membranes of all
cells are lipid-based) and in other areas of the cells that are aqueous, which allows it to
neutralize a wide variety of free radicals. ALA is also capable of donating an electron to
vitamin E molecules that have done their job and are now radicals (though not harmful),
allowing them to function again as antioxidants. Another function of ALA is increasing
cellular glutathione levels, one of the body's most powerful antioxidants. Dr. Packer
eventually demonstrated that ALA fits all four of his criteria, making it one of the most
powerful antioxidants available.

ALA Prevents Nerve Cell Death

One of the downsides of low levels of glutathione is nerve cell death. In the absence of
sufficient levels of glutathione, nerve cells become susceptible to a series of events that
lead to depleted energy supplies and subsequent cell death from starvation. The series of
events is triggered by oxidative stress (in this case excessive activation of NMDA
receptors) and can be ameliorated by increasing the levels of glutathione, which is one of
the benefits of ALA. Consequently, ALA can prevent nerve cell death through its
antioxidant capabilities.

There is also evidence that ALA can minimize or eliminate the neuron (nerve cell) death
associated with taking MDMA (ecstasy). I do not advocate using chemicals that cause
brain cell death, but if you're foolish enough to do such things, be smart enough to protect
yourself. According to one study, ALA taken at roughly double the dosage of ecstasy
(and thirty minutes beforehand) can fully prevent serotonergic defects (death of serotonin
producing neurons) caused by ecstasy (Aguirre, N; et al). These findings might rekindle
interest in MDMA as a therapeutic agent in treating alcoholism, phobias, depressions,
and other psychological problems.

Finally, some studies (in rat models) have indicated that ALA can create new neurites
(new neural cells) and cause existing neurites to be larger and healthier. The studies
suggest that neuronal regeneration in humans may be possible as well, providing a
possible treatment for early stage Parkinson's disease, Lou Gehrig's disease, Alzheimer's
disease, and other age-related neurodegenerative diseases.

ALA and Diabetes

Two of the most serious effects of diabetes are atherosclerosis (hardening of the arteries,
which causes heart attacks) and neuropathy (which can lead to blindness through
destruction of nerve cells in the eyes). Many doctors feel that atherosclerosis is caused
by excessive glycation (long-term changes in blood chemistry due to high glucose levels,
which result from insulin resistance) and that neuropathies are a result of free-radical
damage caused by diabetes (possibly also a result of glycation). As shown above, ALA
can limit the damage from free radicals (preventing neuropathies, but also reducing the
associated pain), and it also can limit the damage from glycation by reducing blood
glucose levels. If taken before insulin resistance becomes pathological, ALA might be
able to correct or prevent insulin resistance entirely.

Most type II diabetics produce more than enough insulin but are not able to use it
effectively. As a result, glucose (blood sugar) levels remain very high for longer periods
of time, as increasing production of insulin is required to remove the glucose from the
blood. The primary storage site for glucose following a meal is muscle tissue, and many
strategies in improving insulin sensitivity are aimed at making muscle tissue more
receptive to the function of insulin.

ALA has been show in many studies to improve glucose uptake by muscle tissue.
Henrickson and associates (Arzneimittelforschung) were the first to show that ALA can
increase the insulin-stimulated glucose disposal in patients with type II diabetes. They
also have shown that, in rat studies, ALA can increase glucose uptake in muscle tissue in
the absence of insulin, a finding that has some support in human trials and much more
support through anecdotal evidence of ALA users.
The evidence is compelling enough that many of us who are concerned with optimal
health have been using ALA for several years now. In fact, some of the leading
nutritional coaches in the sports world have been using ALA with their athletes to
improve glucose uptake (and thus, recovery from workouts or competitions).

Over the long term, early and consistent use of ALA is likely to prevent insulin resistance
and diabetes in the average person who combines an intelligent supplement strategy with
moderately healthy eating.

Recommendations

For most users, 100 mg two to three times a day will have potent antioxidant effects. For
those with insulin resistance, 200 to 300 mg two to three times a day (preferably 20
minutes before a meal) will have positive effects. Please consult with your doctor if you
are being treated for insulin resistance.

Those with diabetes are urged to consult with a physician about adding ALA to the diet.
Do not take ALA without your doctor's involvement. ALA can have dramatic effects on
glucose levels, and if you are using insulin or other diabetes medications this could be a
problem. If your doctor is resistant, find a more enlightened doctor who will work with
you to get you off of prescription medications as much as possible.

For those who are already healthy but like the occasional binge meal and don't want the
negative consequences, a 300 to 600 mg dose before a meal high in simple carbohydrates
can minimize the insulin response. As a side note, research shows that including 14
grams of fiber with a meal of pure glucose (75 grams, the amount used to test for glucose
tolerance as an indicator of diabetes) will nearly eliminate the insulin surge caused by the
glucose. This finding shows that adding fiber supplements or eating fibrous vegetables
can have a positive impact on blood sugar levels.

ALA is truly a remarkable substance and one of the few supplements worth its cost.
Recent advances in the science of ALA have brought the price into the affordable range if
you are willing to shop on the Web for the best price (bulk powders and self-capsulation
are the most affordable option).

A new version of ALA, called r-ALA seems to show promise as a more powerful and
effective derivative, at lower doses, but the substance is new and the research is not yet
conclusive. When more information is available, I will report on it.

William Harryman, MS, CFT, is an ISSA-certified fitness trainer. He is the founder of

Integral Options for Life. For fitness and nutrition consultation, he can be reached at
billharryman@gmail.com, or 520-248-3577.
A Few Relevant Studies Pertaining to Neuropathy

[It is my feeling that ALA is effective for all neuropathies resulting from oxidative stress,
not only those connected to type II diabetes.]

Altenkirch, H., et al. Effects of lipoic acid in hexacarbon-induced neuropathy.

Neurotoxicol Teratol. 12:19-22, 1990.

Hager K, Marahrens A, Kenklies M, et al. Alpha-lipoic acid as a new treatment option for
Azheimer type dementia. Arch Gerontol Geriatr. Jun2001;32(3):275-282.

Nagamatsu, M., et al. Lipoic acid improves nerve blood flow, reduces oxidative stress,
and improves distal nerve conduction in experimental diabetic neuropathy. Diabetes
Care. 18:1160-1167, 1995.

Ziegler, D., et al. Effects of treatment with the antioxidant alpha-lipoic acid on cardiac
autonomic neuropathy in NIDDM patients. A 4-month randomized controlled multicenter
trial (DEKAN Study). Diabetes Care. 20(3):369-373, 1997.
Diabetes Care. 2003 Mar;26(3):770-6.

The sensory symptoms of diabetic polyneuropathy are improved

with alpha-lipoic acid: the SYDNEY trial.
Ametov AS, Barinov A, Dyck PJ, Hermann R, Kozlova N, Litchy WJ, Low PA,
Nehrdich D, Novosadova M, O'Brien PC, Reljanovic M, Samigullin R, Schuette
K, Strokov I, Tritschler HJ, Wessel K, Yakhno N, Ziegler D; SYDNEY Trial
Study Group.

Russian Medical Academy for Advanced Studies, Moscow, Russia.

OBJECTIVE: Because alpha-lipoic acid (ALA), a potent antioxidant, prevents or

improves nerve conduction attributes, endoneurial blood flow, and nerve (Na(+) K(+)
ATPase activity in experimental diabetes and in humans and may improve positive
neuropathic sensory symptoms, in this report we further assess the safety and efficacy
of ALA on the Total Symptom Score (TSS), a measure of positive neuropathic
sensory symptoms. RESEARCH DESIGN AND METHODS: Metabolically stable
diabetic patients with symptomatic (stage 2) diabetic sensorimotor polyneuropathy
(DSPN) were randomized to a parallel, double-blind study of ALA (600 mg) (n = 60)
or placebo (n = 60) infused daily intravenously for 5 days/week for 14 treatments.
The primary end point was change of the sum score of daily assessments of severity
and duration of TSS. Secondary end points were sum scores of neuropathy signs
(NIS), symptoms (NSC), attributes of nerve conduction, quantitative sensation tests
(QSTs), and an autonomic test. RESULTS: At randomization, the groups were not
significantly different by the criteria of metabolic control or neuropathic end points.
After 14 treatments, the TSS of the ALA group had improved from baseline by an
average of 5.7 points and the placebo group by an average of 1.8 points (P < 0.001).
Statistically significant improvement from baseline of the ALA, as compared with the
placebo group, was also found for each item of the TSS (lancinating and burning
pain, asleep numbness and prickling), NIS, one attribute of nerve conduction, and
global assessment of efficacy. CONCLUSIONS: Intravenous racemic ALA, a potent
antioxidant, rapidly and to a significant and meaningful degree, improved such
positive neuropathic sensory symptoms as pain and several other neuropathic end
points. This improvement of symptoms was attributed to improved nerve
pathophysiology, not to increased nerve fiber degeneration. Because of its safety
profile and its effect on positive neuropathic sensory symptoms and other neuropathic
end points, this drug appears to be a useful ancillary treatment for the symptoms of
diabetic polyneuropathy.

Publication Types:
 Clinical Trial
 Randomized Controlled Trial

PMID: 12610036 [PubMed - indexed for MEDLINE]

Vnitr Lek. 2002 Jun;48(6):534-41.

[Autonomic neuropathy in diabetics, treatment possibilities]

[Article in Czech]

Lacigova S, Rusavy Z, Cechurova D, Jankovec Z, Zourek M.

I. interni klinika Fakultni nemocnice, Plzen.

Diabetic neuropathy is a chronic complication of diabetes. It involves non-

inflammatory damage of the function and structure of peripheral nerves by metabolic
vascular pathogenic processes. In case of affection of vegetative nerves (small non-
myelinated C fibres) autonomic neuropathy develops. It is a relatively frequent form
of neuropathy which remains for a long time without clinical symptoms and therefore
is rarely diagnosed and treated. Manifestations of the affection are encountered in all
organs which are supplied by vegetative nerves. The presence of this complication of
diabetes is signalized by tachycardia at rest, deterioration of gastric evacuation,
diabetic diarrhoea or constipation, erectile dysfunction, impaired function of the
sweat glans or impaired pupillary reaction. The advanced form involves the danger of
latent myocardial ischaemia, serious postural hypotension and sudden death. It
increases significantly the mortality of the affected patients. Similarly as the treatment
of other complication of diabetes, treatment of autonomic neuropathy is difficult. The
objective of the present paper is to review contemporary therapeutic possibilities. An
essential prerequisite remain efforts to achieve optimal compensation. The authors
draw attention to the effect of alpha-lipoic acid which exerts a positive effect not only
on subjective symptoms but also on the objective finding. The other mentioned drugs
are used either only experimentally or for purely symptomatic treatment.

Publication Types:
 Review
 Review, Academic

PMID: 12132356 [PubMed - indexed for MEDLINE]

Diabetes Metab Res Rev. 2002 May-Jun;18(3):176-84.

Oxidative stress and diabetic neuropathy: pathophysiological

mechanisms and treatment perspectives.
van Dam PS.

Department of Internal Medicine and Endocrinology, University Medical Center, Utrecht,

The Netherlands. P.S.vanDam@digd.azu.nl

Increased oxidative stress is a mechanism that probably plays a major role in the
development of diabetic complications, including peripheral neuropathy. This review
summarises recent data from in vitro and in vivo studies that have been performed both to
understand this aspect of the pathophysiology of diabetic neuropathy and to develop
therapeutic modalities for its prevention or treatment. Extensive animal studies have
demonstrated that oxidative stress may be a final common pathway in the development of
diabetic neuropathy, and that antioxidants can prevent or reverse hyperglycaemia-induced
nerve dysfunction. Most probably, the effects of antioxidants are mediated by correction
of nutritive blood flow, although direct effects on endoneurial oxidative state are not
excluded. In a limited number of clinical studies, antioxidant drugs including alpha-lipoic
acid and vitamin E were found to reduce neuropathic symptoms or to correct nerve
conduction velocity. These data are promising, and additional larger studies with alpha-
lipoic acid are currently being performed. Copyright 2002 John Wiley & Sons, Ltd.

Publication Types:

 Review

 Review, Tutorial

PMID: 12112935 [PubMed - indexed for MEDLINE]

Dev Pharmacol Ther. 1990;14(3):193-9.

Thioctic acid induces dose-dependent sprouting of neurites in

cultured rat neuroblastoma cells.
Dimpfel W, Spuler M, Pierau FK, Ulrich H.

Pro Science Private Research Institute, Linden, FRG.

Quantitative computer-assisted evaluation of thioctic acid-induced sprouting in

Neuro-2a cells reveals a clear dose dependence with respect to several parameters of
sprouting. At first predominantly the length of main sprouts per cell (neurites from
cell soma to first branching) and the number of branchings per cell are increased.
With the higher dosages, the length of branches per cell rises considerably, too. In
contrast, the degree of branching (mean length of neurites per branching) seems to be
independent of the concentration of thioctic acid. The capacity of thioctic acid to
induce sprouting is discussed in terms of the involvement of SH groups and with
regard to regeneration phenomena as they may occur in diabetogenic neuropathy.

PMID: 2114274 [PubMed - indexed for MEDLINE]