Review Article

Alpha Lipoic Acid for Symptomatic Peripheral Neuropathy in

Patients with Diabetes: A Meta-Analysis of Randomized
Controlled Trials
Presented by : dr. Veny
Supervisor : dr. Theresia Christin, Sp.S

INTRODUCTION
DIABETES MELLITUS

PARESTHESIA

NUMBNESS

PAIN

PERIPHERAL
NEUROPATHY

BACKGROUND
NEUROPHATIC
PAIN

AL
A

LIMITED IN
EFFECTIVENESS
CONSIDERABLE SIDE
EFFECT
NO EFFECT IN CELL
DAMAGE

ANTI-DEPRESSANTS
ANTI-EPILEPTICS
OPIOIDS

BACKGROUND
ALA

STUDY IN HUMAN
- Preventing the damage caused by
hyperglycaemia

ALA

-IMPROVE NERVE FUNCTION

-ANALGESIA EFFECT
-FEW SIDE EFFECT
-APPROVED IN GERMANY

EARLIER META ANALYSIS (2003)

ALA (600 mg/day) in patients with diabetes and
neuropathic pain concluded that three weeks of
treatment with intravenous ALA led to a
significant decrease in reported neuropathic
pain.
However, studies investigating the effect of oral
administration were not included.
In addition, the meta-analysis did not fulfil the
Cochrane methodological criteria for the
systematic reviews.

AIM
To evaluate the effects of intravenous as
well as oral administration of alpha lipoic
acid versus placebo in patients with
symptomatic peripheral diabetic
neuropathy.

Research Design and Methods

OUTCOME MEASURE

STATISTICAL ANALYSIS

LITERATURE SEARCH

STUDY SELECTION

INCLUSION CRITERIA
(1) RCTs on alpha lipoic acid
(2) a study population consisting of
patients with diabetesmellitus and
peripheral neuropathic pain
(3) use of the total symptom score (TSS)
as the outcome measure

METHODOLOGIC QUALITY
ASSESSMENT
Using the standardised evaluation form for
RCTs and systematic reviews developed
by the Dutch Cochrane Centre.
Levels of evidence and recommendation
grades were applied according to the
Oxford Centre of Evidence-based
Medicine.

METHODOLOGIC QUALITY
ASSESSMENT

OUTCOME MEASURE
Using Total Symptom Score (TSS)

STATISTICAL ANALYSIS

Meta-analysis was undertaken using RevMan5 software

(The Nordic Cochrane Centre, The Cochrane Collaboration).

The I2 statistic was used to assess statistical heterogeneity.

An I2 > 30% was considered to denote heterogeneity.
- A random-effect model was used in case of heterogeneity.
- A fixed-effect model in the absence of heterogeneity.

The MantelHaenszel method was subsequently applied to estimate

pooled effect sizes.

RESULTS

The study populations in the four selected RCTs were all made up of
patients with peripheral diabetic neuropathy [1518]
The effects of orally administered alpha lipoic acid were
investigated in two studies and intravenous administration in
another two studies.

RESULTS
The age range was from 18 to 74 years.
Most of the patients included had type 2 diabetes
mellitus.

RESULTS

RESULTS
Dosages 600 mg per day did not result in
a further improvement in the TSS and
resulted in a greater incidence of side
effects; such as nausea, vomiting, and
dizziness.
Dosage 600 mg per day resulted side
effects that were not different than seen
with placebo.

Discussion
Intravenous administration of alpha lipoic
acid leads to significant and clinically
relevant improvements of symptomatic
peripheral diabetic neuropathy in the short
term.
It is unclear if the significant improvements
seen with the oral administration of alpha
lipoic acid are clinically relevant.

Toronto Scoring System

Methycobal mendorong proses mielinisasi

dan transport dari lemak. (in vitro)
(Yonezawa T. et al., 1981)
Mempercepat pemulihan transmisi sinaps
Shibuya et. al.,1981)

Methycobal d1 transport pada tingkatan

tinggi ke dalam organel
dari serabut saraf. (Rat model)
(Inada et.al.,1981)
Methycobal mempercepat sintesis dari
asam nukleat dan protein pada
sel-sel saraf sehingga menstimulasi
regenerasi axon. (Mouse model)
(Nakazawa et.al.,1970)

AUTHOR

DOSIS

DIAGNOSIS

Fuji et al (n=76)

1500 mcg/day, oral

Low back pain, stenosis spinalis,

HNP,

Nemoto et al
(n=19)

500 mcg, injection,

2x/week

Cervical spondilosis,
Lumbalis spondilosis

Koya (n=10)

500 g

Post Herpetic Neuralgia (n=10),

Occipital Neuralgia (n=26),
Trigeminal Neuralgia (n=14)