Name: Alpha lipoic acid, Thiotic acid, ALA
Goes well with: Vitamin B12, Gamma linoleic acid, Omega 3s, Melatonin
Number of scientific references: 48
Level of Evidence: Level III What is this?
Note: ALA , as an antioxidant, shows significant therapeutic potential in treatment of diabetic neuropathy. It is a cost effective treatment for relieving neuropathic pain. It can improve therapeutic outcomes of conventional treatment.
One of the actively researched natural therapeutic agents for neuropathy is Alpha Lipoic Acid (ALA). It is a naturally occurring substance and also known as thiotic acid.
It was first discovered in 1937 by Snell but isolated by Reed in 1951. It’s first clinical use dates back to 1959 where it was employed for treating a case of acute poisoning caused by mushrooms. Soon the authors describing the first clinical use of ALA also reported its benefits in neuropathy.
ALA serves as an essential agent for the functioning of various enzymes involved in oxidative reactions in our body. It is an antioxidant and even it’s reduced form dihydrolipoic acid shares its properties.
Scientific literature proves that it is a potent antioxidant, metal chelator and it also elevates the levels of antioxidant enzymes to improve antioxidant status in the body. It is found to benefit in conditions like diabetes, hypertension, Alzheimer’s disease, cancer, atherosclerosis etc.
Alpha lipoic acid benefits in neuropathy by exerting an antioxidant action, relieving pain and protecting nerve health from toxicity. It has been clinically used for diabetic neuropathy and delivered positive results.
Suggested Alpha Lipoic Acid Supplements For Peripheral Neuropathy
Please consult a health practitioner before taking any health supplements.
I have just updated the article on the ALA and R-ALA supplements and you can read about that below. But here is a short summary:
- ALA racemic mixture (contains both R- and S- form) has been successfully used in clinical studies to relieve neuropathy symptoms.
- R-ALA standalone is said to be more potent than S-ALA and may deliver effects equivalent to the racemic or conventional ALA at a lower dose.
- R-alpha lipoic acid is more bioavailable than S-Alpha Lipoic Acid but it is unstable.
- Presence of S-Alpha Lipoic Acid in the racemic mixture improves the stability of the R-enatiomer.
- Stabilised R-Alpha Lipoic Acid is prepared in the form of sodium salt or cyclodextrin complex.
- Stabilised R-ALA supplements are more expensive than the racemic mixture.
Based on the literature currently available, you can opt for either conventional Alpha Lipoic Acid or stabilised R-Alpha Lipoic Acid for neuropathy treatment depending on your requirements.
Alpha Lipoic Acid (Racemic mixture) supplements
These contain both R- and S- form of alpha lipoic acid. Start with small doses and increase gradually.
|Doctor’s Best Alpha Lipoic Acid|
It contains 600mg racemic mixture ALA. They are soy and gluten free, vegetarian capsules.
Dosage: 600mg a day
Stabilised R-ALA supplements
The stabilised form of R-Alpha Lipoic Acid available in the market today is Bio-Enhanced® R-Lipoic Acid developed by Geronova Research, Inc.(Buy from Amazon). It is a sodium salt of Alpha Lipoic Acid.
Here are a few dietary supplements that contain Bio-Enhanced® R-Lipoic Acid. Some may contain additional vitamins, so please read the complete ingredient list of the supplement before purchasing.
Dosage: 300mg or Follow manufacturer’s dosage
|Thorne Research R-Lipoic Acid||Doctor’s Best Stabilized R-Lipoic Acid|
Image Credit:Thorne Research, Inc.
Image Credit: Doctor’s Best
|It contains 300mg R-Lipoic Acid packed in vegetarian capsules.||It contains 100mg R-Lipoic Acid packed in vegetarian capsules.|
5 Proven Benefits Of Alpha Lipoic Acid For Neuropathy
Let’s go through the various research studies that have found ALA beneficial in peripheral neuropathy.
Table of Contents
- 1 Suggested Alpha Lipoic Acid Supplements For Peripheral Neuropathy
- 2 5 Proven Benefits Of Alpha Lipoic Acid For Neuropathy
- 2.1 1. Alpha lipoic acid is a natural antioxidant that protects nerve health
- 2.2 2. Alpha lipoic acid can relieve neuropathic pain
- 2.3 3. It is a neuroprotective agent and benefits in neurotoxicity
- 2.4 4. ALA is clinically proven to be safe and effective in diabetic neuropathy
- 2.5 5. It can benefit in cancer chemotherapy-induced neuropathy
- 3 ALA vs. R-ALA: Which is better for peripheral neuropathy?
- 4 Dosage of Alpha Lipoic Acid For Neuropathy
- 5 Precautions with ALA use
- 6 Conclusion
1. Alpha lipoic acid is a natural antioxidant that protects nerve health
Oxidative stress or imbalance between proxoidant and antioxidant agents in the body is identified as one of the causative factors of neuropathy.
High levels of glucose in diabetes create systemic oxidative stress, and this can damage nerve cells. The experimental study suggests that alpha lipoic acid, as an antioxidant, reduces such damage to nerve cells in diabetic neuropathy.
Pitel et al. conducted an interesting study where they compared the effect of different fatty acids on prevention of neuropathy. The premise of the study was that a deficiency in essential fatty acids contributes to the development of diabetic neuropathy.
The comparison was between DHA and a combination of GLA and ALA. Gamma-linoleic acid (GLA) is an omega six fatty acid while Docosahexaenoic acid (DHA) is an omega three fatty acid.
The GLA-ALA combination completely prevented diabetic neuropathy while DHA showed only a partial response. The difference in effect was attributed to ALA’s antioxidant action.
Similarly, alpha lipoic acid’s antioxidant action is beneficial in chemotherapy-induced neuropathy as it protects the nerve cells from toxicity caused by chemotherapeutic agents.
Quick Gist: Alpha lipoic acid’s antioxidant action helps protect nerve health from toxicity and supports recovery from nerve injury. The antioxidant property of ALA explains its protective action in diabetic and chemotherapy-induced neuropathy.
2. Alpha lipoic acid can relieve neuropathic pain
This analgesic action also extends to neuropathic pain. Maglione et al. state that neuropathy patients experience reduction in pain-related symptoms such as pain intensity, burning sensations and superficial pain after taking ALA.
Allodynia is a pain in response to a stimulus that does not cause pain. A recent study published in Pharmacology research and perspectives, 2015 revealed that ALA has anti-allodynic property and reduces neuropathic pain.
The review study by Mijnhout et al. reveals that intravenous therapy with ALA daily for three weeks brings about a significant and clinically relevant reduction in neuropathic pain in diabetic neuropathy.
Vasudevan et al. showed that alpha lipoic acid and vitamin B12 as an add-on therapy to pregabalin aids in reducing neuropathic pain and improves sleep and nerve function in diabetic neuropathy.
Quick Gist: Research shows that alpha lipoic acid has analgesic activity and can reduce neuropathic pain by reducing oxidative stress and strengthening nerve function.
3. It is a neuroprotective agent and benefits in neurotoxicity
Thiols are a type of chemical compound, and they hold special relevance concerning antioxidant defences of the brain and other tissues. Glutathione is one such thiol that is responsible for the brain’s antioxidant defence.
Similarly, alpha lipoic acid is a thiol antioxidant and has a neuroprotective action. Alpha lipoic acid crosses the blood brain barrier and strengthens antioxidant defences of the brain.
A recent study published in Biomed Research International, 2013 showed that ALA exerts a neuroprotective action in entrapment neuropathy. It protects neurons and astrocytes (cells that support neurons) from cell death in response to nerve injury.
Exposure to toxins at work or from the environment can contribute to toxic neuropathy. Such toxins that damage the nervous system are referred to as neurotoxins.
Quick Gist: Alpha lipoic acid is a neuroprotective agent- it protects the brain and nervous system by strengthening antioxidant defences. It protects from potential neurotoxins such as environmental toxins, toxic states that develop as a result of health conditions or due to adverse effects of medications.
4. ALA is clinically proven to be safe and effective in diabetic neuropathy
Alpha lipoic acid is an insulin-mimetic and benefits in diabetes by regulating insulin levels, boosting antioxidant defences and reducing inflammation.
A study published in Journal of Diabetes and Metabolic Disorders, 2014 compared the effects of conventional therapy- carbamazepine and pregabalin with alpha-lipoic acid in diabetic neuropathy.
All groups showed a reduction in neuropathic pain, but the fastest pain relief was delivered by pregabalin followed by alpha lipoic acid.
Ruessmann et al. conducted a very interesting study on real-world effects of switching from alpha lipoic acid to conventional symptomatic treatment in diabetic neuropathy.
443 patients were treated with ALA for an average of 5 years. Then the treatment was stopped, 293 patients were started with gabapentin and the rest 150 remained untreated as they did not have significant symptoms.
Out of the 150 who were untreated, 110 developed neuropathy symptoms within two weeks of cessation of ALA therapy.
The statistics in the gabapentin group was as follows:
• 131 individuals stopped treatment due to side effects
• 131 individuals responded to the treatment
• 161 did not respond to the treatment
Visits to the doctor were 3.8 times per 3 months when treated with ALA, and that increased to 7.9 per 3 months when treated with gabapentin or like medications. Also, the monthly cost for ALA was less than that of conventional medicines.
Researchers concluded that switching from alpha lipoic acid to pain relief medicines can be an expensive decision both regarding cost and patient’s health.
Cardiac autonomic neuropathy is a serious complication of diabetes wherein nerve fibres linked to the heart are damaged. Research suggests that alpha lipoic acid (600-1200mg/day orally) can help in counteracting this complication.
Let’s go over a few research studies that have examined the benefits and safety of ALA in diabetic neuropathy. There are many studies, but for the sake of simplicity and ease of understanding, I have included those after the year 2000.
Dosage and Time of ALA therapy
|SYDNEY study, 2003||Ametov et.al||600mg ALA daily IV for five days a week for 14 treatments||Significant reduction in pain, burning sensation and numbness was observed|
|SYDNEY II study, 2006||Ziegler et.al||600-1800mg ALA daily for five weeks||Reduction in stabbing pain and burning sensations was observed; 600mg daily was found to be an effective dose|
|NATHAN I study, 2011||Ziegler et.al||600mg ALA daily for four years||ALA prevented progression of neuropathy and resulted in modest but clinically significant improvement|
|Medical Archives, 2013||Ibrahimpasic K||Dose not mentioned, four months of therapy||ALA’s effect on neuropathy was more pronounced in patients with better blood sugar control; pins and needles type of sensations and night pain reduced|
|Annals of Indian Academy of Neurology, 2014||Vasudevan et.al||75 mg pregabalin, 750 microgram vitamin B12 (methylcobalamin) and 100mg ALA for 12 weeks||Combination therapy resulted in significant improvement in sleep, pain and nerve function.|
|Journal of Diabetes Research, 2015||Garcia-Alcala et.al||1800mg ALA per day for four weeks followed by 600mg daily or cessation of treatment||Symptoms of diabetic polyneuropathy reduced with high dose treatment followed by low dose.
Cessation of ALA increased use of painkillers
|NATHAN 1 proceedings, 2016||Ziegler et.al||600mg ALA daily for four years||Prevention of disease progression, improvement in neuropathy and metabolic health was observed.
ALA therapy improved heart health as well.
|Han et.al||Treatment with Methylcobalamin or ALA was provided for two weeks||Methylcobalamin reduced numbness, abnormal sensations and pinprick sensations better than ALA
ALA was effective in boosting antioxidant defences, burning and pain
Quick Gist: Alpha lipoic acid has been clinically proven to benefit in diabetic neuropathy. Depending on the severity of the condition, patients may require intravenous therapy or oral therapy.
A dose of 600mg ALA daily is found to be safe and effective. It helps reduce pain and other neuropathy symptoms such as burning sensation, numbness, pin and prick sensations.
Combining it with methylcobalamin or with pregabalin and conventional medicines can help reduce the effective dose of alpha lipoic acid and improve therapeutic outcomes.
5. It can benefit in cancer chemotherapy-induced neuropathy
An experimental study showed that combining monosodium glutamate with antioxidants like resveratrol, alpha lipoic acid or CoQ10 helped exert a neuroprotective action against cisplatin induced neuropathy.
Guo et al. found alpha lipoic acid ineffective in preventing neurotoxicity caused by oxaliplatin and cisplatin.
However, a recent study published in Medical Oncology, 2017 found a proprietary blend containing ALA effective in reducing pain and impairment caused by cancer-induced neuropathy.
Quick Gist: Experimental studies suggest that ALA can protect from potential neurotoxicity caused by chemotherapeutic agents, but more research in the form of human trials are necessary to confirm its effectiveness.
ALA vs. R-ALA: Which is better for peripheral neuropathy?
(Update 2018)Alpha Lipoic Acid exists in two forms:
- R-ALA: the natural form
- S-ALA: the synthetic form
Most ALA supplements have a racemic mixture (50/50 mixture) of R- and S- forms and these have been utilised and proven to be effective in clinical studies to date. R- enatiomer is found to better absorbed in the body than S-enatiomer but it is highly unstable. The presence of S-ALA improves its stability and absorption.
However, researchers have been focusing on increasing the stability of R- enatiomer and have developed forms such as R-ALA and Sodium salt and R-ALA and cyclodextrin complex. R-Alpha Lipoic Acid standalone is said to be more potent than S-Alpha Lipoic Acid and may deliver effects equivalent to the racemic or conventional Alpha Lipoic Acid at a lower dose.
R-Alpha Lipoic Acid supplements are expensive than S-Alpha Lipoic Acid.
Most research on Alpha Lipoic Acid and peripheral neuropathy has demonstrated benefits with use of racemic mixture; more studies are required on the efficacy of R-enatiomer in neuropathy. Since both, the racemic mixture and R-ALA, are equally effective in relieving neuropathy symptoms (and also based on the evidence currently available), there is no issue with using either of them.
Dosage of Alpha Lipoic Acid For Neuropathy
Based on the research studies conducted till date, 600mg ALA (racemic: R and S form) daily for 3-6 months is found to be safe and effective. Higher doses have been utilised, but they result in side effects.
There has been one study that used R-Alpha Lipoic Acid (as Liponax solution) for peripheral neuropathy successfully at a dose of 300mg per day for 4 weeks.
In severe cases of diabetic neuropathy, some may require intravenous alpha lipoic acid therapy before oral supplementation.
Combining oral alpha lipoic acid with vitamin B12 (methylcobalamin) may have a synergistic therapeutic action.
ALA’s absorption may be hindered if combined with food. It should be taken 30 minutes before a meal or in a fasted state.
Consult a health practitioner before taking alpha lipoic acid supplements.
Precautions with ALA use
No upper limit of ALA intake has been recommended for humans. Some studies have used doses as high as 1800-2400mg and have not reported serious side effects.
But in some cases, gastric side effects have been noted at the high dose. These include nausea, vomiting, abdominal pain and dyspepsia.
A four-year study examining the benefits of alpha lipoic acid in neuropathy reported serious side effects that affected heart health and were also described as urinary in nature.
There has been a case report describing the development of autoimmune insulin syndrome with ALA supplementation. It is important to note this adverse effect, and it is advisable to work with your health practitioner about the same.
A few cases of itching skin, skin ulceration and bronchitis have been reported at high dose ALA.
One evidence suggests that alpha lipoic acid may be safe for treating neuropathy in pregnancy but more research is required to confirm this.
UMM states alpha lipoic acid should be avoided in case of vitamin B1 deficiency. They report that ALA could have possible drug interactions with diabetes medicines, thyroid medications, chemotherapy and vitamin B1.
Please consult a health practitioner before taking alpha lipoic acid supplements.
Alpha lipoic acid combines antioxidant and neuroprotective activities in neuropathy treatment. Most research to date has found it effective in managing in diabetic neuropathy.
ALA also relieves neuropathic pain and is found to be safe and cost-effective than other medications that aid in pain relief.
It is found to be safe on short-term (maximum 6 months). But it’s cessation results in relapse or return of the symptoms within two weeks.However this single drawback cannot undermine its therapeutic potential in relieving neuropathic pain.
More research is required to ascertain alpha lipoic acid’s effectiveness when combined with other therapeutic agents and also whether it is safe on the long term.
Adding vitamin B12 to alpha lipoic acid therapy must be studied further. Also coupling ALA’s antioxidant action with a potent neuroprotective agent may deliver faster and sustainable results.
Please consult your health practitioner before taking ALA supplements for neuropathy.