Amount of Evidence: High Potential Benefits: High Safety: High
TABLE OF CONTENTS
What is ALA?
In the health community, ALA can mean two things: alpha-linoleic acid (a plant-based form of omega 3) and alpha-lipoic acid, which we are going to look at in this article. Alpha-lipoic acid is a potent antioxidant and a compound involved in energy metabolism. Some people, including longevity researcher David Sinclair, believe that ALA holds great potential as an anti-aging supplement. In this article, we will look at ALA’s main benefits, potential side effects, and how to use it the right way.
Potential benefits
It is important to note that all of the potential benefits mentioned below are dose-dependent. In general, the higher the dose you take, the more pronounced the effects will be. However, they do reach a plateau at a certain point. We will discuss the best dosing protocol later in this article.
Major benefits
Proper mitochondria functioning – As we age, our mitochondria function becomes worse and worse. While this hasn’t yet been proven by strong evidence, ALA likely protects our mitochondria from aging. This is why it may be a promising anti-aging supplement.
Heavy metal chelation – Alpha-lipoic acid can bind to heavy metals like mercury and arsenic and helps flush them out of the body. If you are going to use ALA for the purpose of heavy metal chelation, be sure to take the supplement every 3-4 hours, including at night, to prevent heavy metal reaccumulation. Andy Cutler, an expert at mercury detoxification, recommends starting with 25-50 mg of ALA every 3 hours for 3-4 days with at least a 4-day break in between and gradually building your way up to 200 mg every 3 hours. The S-form is usually better for this purpose than the R-form. For more information on using ALA for heavy metal detoxification, please read Andy Cutler’s book The Mercury Detoxification Manual before going through this protocol.
Minor benefits
Reduced general oxidation – ALA is proven to act as an antioxidant and reduces the biomarkers of general oxidation and lipid peroxidation. Unfortunately, there may not be a correlation between this effect and overall health.
Improved HRV – Alpha-lipoic acid appears to cause positive changes in heart rate variability.
Weight loss – Very high doses (1500+ mg) seem to help obese people lose weight. This effect likely applies to individuals at a healthy weight or those who are slightly overweight.
Reduced claudication during exercise – Intermittent claudication during exercise can lead to problems such as cramping, numbness, pain, tingling, and weakness. ALA appears to be very effective at reducing claudication.
Reduced symptoms of diabetic neuropathy – Alpha-lipoic acid is able to notably reduce nerve pain associated with diabetes.
Lowered HbA1c – This effect appears to be minor.
Lowered inflammation – While the evidence is mixed, ALA appears to be able to lower inflammation, at least to some extent.
Metal chelation – ALA acts as a metal chelator and can help you detoxify from heavy metals.
Creatine absorption – Alpha-lipoic acid helps creatine enter muscle cells. Thus, ALA is shown to increase muscle creatine content.
Improved nerve regeneration – ALA appears to aid nerve repair and can be especially helpful in this regard to those who are experiencing a nervous system injury. For healthy individuals, the potential improvement is tiny.
Increased blood flow – While the effect is not significant, alpha-lipoic acid was shown to increase blood flow in two studies.
Unproven benefits
The effect of ALA on these parameters is either not sufficiently researched or the science shows little to no efficacy in these areas.
Cancer prevention – While this effect needs to be proven by more research, ALA may be effective for reducing the risk for certain types of cancer, such as breast cancer.
CRP (C-reactive protein) – While ALA does seem to lower inflammation in general, it doesn’t seem to have any effect on CRP in most people.
Blood pressure – The effect of alpha-lipoic acid on blood pressure is not significant.
Heart rate – ALA does not directly influence your heart rate.
Antioxidant enzyme profile – The effects on antioxidant enzymes are mixed. A few studies show a decrease in glutathione peroxidase and an increase in catalase. ALA doesn’t seem to affect SOD.
Blood glucose – Only a tiny reduction was noted in one study.
Insulin sensitivity – No meaningful effect on insulin sensitivity was ever noted.
Cognitive decline – The effect of ALA on cognitive decline and neurodegenerative diseases (such as dementia) has been studied but not yet proven.
Possible side effects
These side effects are dose-dependent and the risk for them increases (most often linearly but sometimes exponentially) as the dose is increased. Some of the side effects are relevant only at very high doses.
An imbalance in antioxidants – If you are a healthy person with a good antioxidant balance, ALA’s antioxidant effects could do more harm than good.
Nausea – This effect is minor and by no means dangerous.
Itching sensation – Higher doses of ALA (1-2 grams) can make your skin itchy.
Oxidation of LDL – This effect has only been shown in one study so far and mainly seems to impact people who do not exercise.
Heavy metal reaccumulation – Alpha-lipoic acid is a potent heavy metal chelator and taking high doses at once can lead to heavy metal reaccumulation. To prevent this, it is best to spread your doses evenly throughout the day. You preferably want to take ALA every 3 hours to prevent this side effect.
Mercury poisoning – Amalgam contains mercury, a harmful heavy metal that can leach into the blood. ALA can speed the leaching process up by pulling the mercury out of your fillings into your bloodstream and organs. If you have amalgam fillings, make sure to get them removed before taking alpha-lipoic acid.
Mineral deficiencies – This effect only applies to high doses (2+ grams a day) and is caused by the metal-chelating properties of ALA. If you take regular doses, you do not have to fear that you will become deficient in minerals because of the supplement.
ALA toxicity – While this is by no means a concern if you stick to regular doses, ALA could be toxic at extremely high doses and even lead to death.
Who should not take ALA?
You should probably avoid taking alpha-lipoic acid if you:
have amalgam fillings – Amalgam contains mercury, a harmful heavy metal that can leach into the blood. ALA can speed the leaching process up by pulling the mercury out of your fillings into your bloodstream and organs. If you have amalgam fillings, make sure to get them removed before taking alpha-lipoic acid.
are a healthy individual – The most significant benefits associated with ALA do not seem to apply to healthy people. For example, ALA is shown to protect the nerves of diabetics but it probably doesn’t for those who don’t have diabetes.
are on a budget – Even though ALA is not the most expensive supplement, there are way more cost-effective supplements on the market.
Who will benefit the most?
You should definitely consider taking ALA if you:
experience intermittent claudication when you exercise – If you experience cramping, numbness, pain, tingling, or weakness during exercise, ALA might help with this problem.
have high levels of heavy metals in your body – ALA can effectively and reliably help you detoxify from most heavy metals.
suffer from diabetic neuropathy – Alpha-lipoic acid can greatly reduce the symptoms.
have a high budget for supplements – Even though the benefits of ALA may not be too significant, the supplement is so safe that the benefits should outweigh the potential side effects in the vast majority of people.
Forms of ALA
There are 3 different forms of alpha-lipoic acid:
Alpha S-lipoic acid – This synthetically produced form can be found in most supplements that are labeled as ALA. Unfortunately, the S form is not very bioavailable as only around 30% gets absorbed in the body. It is also more likely to cause unwanted side effects (even though it still is pretty safe). The main benefit of this form other than the price is that it can be safer and possibly more effective at chelating heavy metals.
Alpha RS-lipoic acid – The RS form is a combination of the S and R forms and can also be labeled as ALA.
Alpha R-lipoic acid – This is the best form of ALA. Commonly sold as R-lipoic acid, this form is more bioavailable and also appears to have a lower side effect profile. This is the natural form of lipoic acid and the only version that exists in nature and is endogenously produced in the body.
How much ALA should you take?
Most of the studies that were done on ALA use doses of 300-600 mg taken once a day.
While you could probably derive slightly more benefits from a higher dosage, 500-600 mg appears to be the best amount to take.
Because the R form is more bioavailable than the S form, you probably need less of it to derive most of the benefits (around 300 mg should be enough).
While ALA is not toxic unless you take doses many dozen times higher, taking more than 600 mg is unnecessary and could cause more harm than good.
It is important to note that the effects of ALA are cumulative. Therefore, you need to take it on regular basis to notice long-term benefits.
Best time to take ALA
Alpha-lipoic acid is a potent heavy metal chelator and taking high doses at once can lead to heavy metal reaccumulation.
To prevent this, it is best to spread your doses evenly throughout the day. You preferably want to take ALA every 3 hours to prevent this side effect.
Another important thing to keep in mind is that the absorption of alpha-lipoic acid gets significantly decreased when you take it with food. Therefore, you want to take the supplement at least 30 minutes before or 2 hours after eating.
Alpha-lipoic acid is also more bioavailable when you take it with water (it is both fat-soluble and water-soluble).
Whether you take ALA in the morning or the evening doesn’t have a significant impact on its effects if any.
Interactions with other supplements
Creatine Alpha-lipoic acid helps creatine enter muscle cells. Thus, ALA is shown to increase muscle creatine content.
CoQ10 This combination work synergistically in supporting mitochondrial function.
L-Carnitine The combination is great for increasing mitochondrial density and mRNA levels in mitochondria.
Vitamin B5 Pantothenic acid (vitamin B5) supplements may decrease ALA’s antioxidant effects, which may increase your need for ALA.
Biotin An amino acid called avidin (found primarily in raw egg whites) is shown to reduce the levels of biotin in your body. It can also do this to ALA. A theory is that when you have enough biotin in your system, avidin will rather bind to it than to alpha-lipoic acid. Thus, your ALA levels should not decrease as much when you consume avidin.
Where to buy ALA
Wherever you decide to buy ALA, remember that the R form is generally superior to the S and RS forms.
Amazon seems to be the best option for ordering ALA supplements in most countries. They offer some very affordable products that are backed by many positive reviews. Also, you can choose from a wide range of brands there without having to spend time searching through other markets on the internet.
One thing to pay attention to if you decide to buy alpha-lipoic acid in capsule form is that some brands display the dosage per serving and not per pill or capsule. Therefore, you may accidentally buy something that is less potent than you intended. Do not fall for this marketing trick.
FAQ
It is not yet known if you develop a tolerance for ALA over time. For this reason, it is best to cycle the supplement and not take it every once in a while. For example, you can take it on weekdays and not take it during the weekend.
Yes. Vitamin C doesn’t impact your sleep in any negative way.
Alpha-lipoic acid can lose potency over time. Fortunately, there is a case to be made that it loses potency slower than other supplements.
Keep your supplements in a cold, dark, and dry place and they will remain just as potent for many years.
It takes around a month to start noticing the benefits of ALA. It is important to note that the effects of ALA are cumulative. Therefore, you need to take it on regular basis to notice long-term benefits.
Vegetables, fruits, and meat are the richest food sources of alpha-lipoic acid. However, the amounts in either of these are so tiny they are not going to have a significant impact on your health.
The half-life of ALA is about 3 hours. Alpha-lipoic acid serum levels peak 50-90 minutes after you take the supplement. After 5 hours, there is no detectable difference in serum ALA.
While ALA is not toxic unless you take doses many dozen times higher, taking more than 600 mg is unnecessary and could cause more harm than good.
Most of the alpha-lipoic acid on the market is vegan-friendly. However, this isn’t always the case and some brands sell animal-based alpha-lipoic acid.
No, it doesn’t. ALA does not interfere with fasting in any notable way.
References
Most of the information provided in this guide is based on scientific research that can be found and verified in the PubMed medical library. We excluded from consideration studies that are either confounded or have a high conflict of interest.
Anecdotal evidence (from reports on Reddit, YouTube, and other sources) is also taken into account unless it contradicts scientific research.
