Latest / Glaucoma, Vision & Longevity: Supplements & Science / Alpha-lipoic acid: Oxidative stress, neuropathy, and glycemic control

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Alpha-lipoic acid: Oxidative stress, neuropathy, and glycemic control · Glaucoma, Vision & Longevity: Supplements & Science

• 0:00
  SPEAKER_00: Introduction Alpha lipoic acid ALA is a powerful antioxidant vitamin-like compound found naturally in foods like spinach and broccoli and sold as a dietary supplement.
• 0:10
  SPEAKER_00: It can neutralize damaging free radicals and help regenerate other antioxidants like vitamins C and E, acting as a cleanup crew against oxidative stress.
• 0:21
  SPEAKER_00: These properties have made ALA of great interest for protecting nerves in chronic diseases such as glaucoma and diabetes.
• 0:28
  SPEAKER_00: Glaucoma involves slow loss of the optic nerve cells, retinal ganglion cells, often aided by oxidative damage, while diabetes causes high blood sugar and nerve damage.
• 0:39
  SPEAKER_00: In this article, we review the evidence on ALA's effects in the eye and in blood sugar control and discuss safety considerations.
• 0:46
  SPEAKER_00: ALA for glaucoma, reducing oxidative stress and protecting nerves.
• 0:50
  SPEAKER_00: In glaucoma, damage to the optic nerve is linked not only to high eye pressure, but also to reduced blood flow and oxidative stress in the retina.
• 0:59
  SPEAKER_00: In fact, experts note, vascular factors may have important roles in the pathophysiology of glaucoma, underlining the need to measure and improve ocular blood flow.
• 1:09
  SPEAKER_00: ALA as an antioxidant can help counter these processes.
• 1:14
  SPEAKER_00: Laboratory studies show promising neuroprotective effects of ALA in glaucoma models.
• 1:19
  SPEAKER_00: In one well-known study, mice prone to glaucoma were fed ALA in their diet.
• 1:24
  SPEAKER_00: The treated mice showed higher expression of antioxidant genes and proteins in the retina, with lower levels of oxidative damage markers, damaged lipids, proteins, and DNA compared to controls.
• 1:37
  SPEAKER_00: These mice also had better survival of retinal ganglion cells.
• 1:40
  SPEAKER_00: After months of treatment, the ALA-fed mice had healthier optic nerves and about 13% more optic nerve axons than untreated mice.
• 1:49
  SPEAKER_00: In other words, ALA slowed the loss of nerve fibers in glaucoma.
• 1:53
  SPEAKER_00: The researchers concluded that ALA reduces oxidative stress and improves RGC retinal ganglion cell survival in glaucoma.
• 2:00
  SPEAKER_00: Clinical data in human glaucoma patients is still sparse, but some results are encouraging.
• 2:06
  SPEAKER_00: For example, a small six-month study gave glaucoma patients a supplement containing R alpha-lipoic acid, the active form of ALA, plus other antioxidants, vitamin C, E, lutein, omega-3, etc.
• 2:18
  SPEAKER_00: After six months, the patients had significantly higher blood antioxidant capacity and much lower levels of melondialdehyde, a blood marker of oxidative damage.
• 2:28
  SPEAKER_00: They also reported improved tear production, important for ocular surface health, and fewer dry eye symptoms.
• 2:35
  SPEAKER_00: Importantly, the supplement was well tolerated with no reported side effects or intolerances.
• 2:41
  SPEAKER_00: The authors noted that the antioxidant formula counteracted oxidative stress and stabilized the functional parameters of the ocular surface and the glaucoma without adverse effects.
• 2:53
  SPEAKER_00: While this study included other nutrients beside ALA, it supports the idea that using ALA in a glaucoma-safe formula can boost antioxidant defenses in the eye.
• 3:04
  SPEAKER_00: Animal and human studies together suggest ALA can help protect ocular nerves by reducing oxidative stress.
• 3:11
  SPEAKER_00: Future clinical trials should look for objective eye measures of benefit.
• 3:15
  SPEAKER_00: For example, optical coherence tomography can measure the thickness of the retinal nerve fiber layer, RNFL.
• 3:22
  SPEAKER_00: A thinner RNFL indicates nerve loss in glaucoma.
• 3:25
  SPEAKER_00: Inman et al.
• 3:27
  SPEAKER_00: showed ALA helped preserve optic nerve fibers in mice, so in patients, one could test whether ALA slows RNFL thinning on OCT.
• 3:35
  SPEAKER_00: Likewise, improved optic nerve blood flow could be an endpoint.
• 3:38
  SPEAKER_00: Newer techniques like OCT angiography measure tiny retinal blood vessels.
• 3:42
  SPEAKER_00: Indeed, glaucoma patients have significantly reduced peripapillary blood flow indexes on OCTA, so an increase in these blood flow measurements would be a useful sign of improved ocular perfusion.
• 3:55
  SPEAKER_00: In short, changes in ocular perfusion by imaging or Doppler and in RNFL thickness would be key endpoints to watch in eye studies of ALA.
• 4:04
  SPEAKER_00: LA in diabetes, blood sugar control, and neuropathy.
• 4:08
  SPEAKER_00: Aside from eye disease, ALA is widely studied in diabetes, especially for diabetic neuropathy, nerve pain.
• 4:15
  SPEAKER_00: It also affects blood sugar levels.
• 4:17
  SPEAKER_00: ALA improves insulin sensitivity and helps cells take up glucose, so it can modestly help lower blood sugar.
• 4:24
  SPEAKER_00: Several human trials and reviews have tested ALA in type 2 diabetes.
• 4:28
  SPEAKER_00: A 2022 meta-analysis of 16 randomized trials, total 1,000 patients, found that each additional 500 mg per day of ALA produced statistically significant drops in hemoglobin A1C, average blood sugar, and fasting glucose.
• 4:44
  SPEAKER_00: In other words, increasing the daily ALA dose by 500 mg lowered A1C by about 0.3 percentage points, and also reduced weight, inflammation, CRP, and triglycerides.
• 4:56
  SPEAKER_00: These findings are notable, but the actual changes in blood sugar were relatively small.
• 5:01
  SPEAKER_00: Another comprehensive review noted that, in routine clinical trials, ALA's effect on A1C tends to be limited or inconsistent.
• 5:10
  SPEAKER_00: Many studies, often with low doses or short duration, found no significant changes in A1C.
• 5:16
  SPEAKER_00: For example, some trials saw mild A1C improvement only at high doses, while others saw no change.
• 5:23
  SPEAKER_00: Overall, these authors concluded that ALA's benefits for long-term sugar control and diabetics are promising but mixed.
• 5:30
  SPEAKER_00: The bottom line for patients: ALA can support blood sugar control, but it is not a substitute for diabetes medications.
• 5:36
  SPEAKER_00: If you have type 2 diabetes, adding ALA, typically 600 to 1200 milligrams daily, may slightly improve blood sugar and help with weight markers, but results vary.
• 5:48
  SPEAKER_00: Its more established use is for diabetic neuropathy.
• 5:51
  SPEAKER_00: Multiple trials have shown that ALA, usually 600 to 1200 mg IV or oral, significantly improves nerve conduction and reduces neuropathy symptoms.
• 6:01
  SPEAKER_00: Many diabetic patients take ALA for nerve pain relief in practice.
• 6:06
  SPEAKER_00: Safety and drug interactions.
• 6:08
  SPEAKER_00: After eye surgery, trabeculectomy, there is little direct data on ALA for patients after glaucoma surgery.
• 6:14
  SPEAKER_00: However, an animal study is reassuring.
• 6:17
  SPEAKER_00: In rabbits undergoing trabeculectomy, a common glaucoma surgery, adding ALA eye drops was well tolerated.
• 6:23
  SPEAKER_00: Over four weeks, no rabbits developed infection, cataract, or inflammation from the ALA drops.
• 6:29
  SPEAKER_00: The treated group even had better surgical bleb survival than untreated controls.
• 6:34
  SPEAKER_00: Fewer blebs failed.
• 6:36
  SPEAKER_00: In other words, topical ALA appeared safe and possibly beneficial for wound healing after trabeculectomy in this model.
• 6:43
  SPEAKER_00: While human studies are needed, this suggests that using ALA, especially topically, after surgery is unlikely to hurt and may reduce scar tissue.
• 6:52
  SPEAKER_00: Of course, any supplement after surgery should be discussed with the surgeon.
• 6:57
  SPEAKER_00: Hypoglycemia risk.
• 6:58
  SPEAKER_00: Because ALA enhances insulin action, diabetic patients or those on diabetes drugs should watch for low blood sugar.
• 7:05
  SPEAKER_00: Health agencies have noted rare cases of ALA triggering an insulin autoimmune syndrome, IAS, in susceptible people.
• 7:13
  SPEAKER_00: In IAS, the body makes antibodies to insulin, causing unexpected low blood sugars.
• 7:18
  SPEAKER_00: These cases were often genetic and mostly reported in East Asian patients.
• 7:23
  SPEAKER_00: Importantly, all of the reported hypoglycemia cases resolved after stopping ALA.
• 7:28
  SPEAKER_00: In practical terms, if you take ALA with insulin or sulfonylureas, monitor your blood sugar, especially when starting or increasing the dose.
• 7:37
  SPEAKER_00: Symptoms of hypoglycemia, sweating, dizziness, confusion should prompt stopping ALA and contacting a doctor.
• 7:43
  SPEAKER_00: This side effect is very rare, but worth knowing about if you have diabetes.
• 7:48
  SPEAKER_00: Thyroid medication.
• 7:49
  SPEAKER_00: Some lab studies suggest ALA might interfere with thyroid hormone.
• 7:53
  SPEAKER_00: Levothyroxine, T4, is converted in the body to its active form T3, and animal data indicate ALA can slow that conversion.
• 8:02
  SPEAKER_00: In practice, this is a theoretical concern.
• 8:05
  SPEAKER_00: People on thyroid medication should tell their doctor if they start ALA.
• 8:09
  SPEAKER_00: It may be prudent to take the thyroid pill and ALA at different times of day and to have periodic thyroid blood tests, although strong evidence of a problem is lacking.
• 8:20
  SPEAKER_00: Chemotherapy and other drugs.
• 8:22
  SPEAKER_00: ALA's antioxidant action raises questions for patients on chemotherapy.
• 8:27
  SPEAKER_00: Some oncologists worry antioxidants might reduce chemotherapy effectiveness, since certain chemo drugs kill cancer cells via oxidative damage.
• 8:36
  SPEAKER_00: Research is mixed.
• 8:37
  SPEAKER_00: Hello pharmacist notes that any ALA chemotherapy interaction is theoretical.
• 8:41
  SPEAKER_00: Alpha lipoic acid's antioxidant activity might in theory change how well these cancer treatments work, though experts disagree.
• 8:50
  SPEAKER_00: In fact, some clinical trials have even given ALA to cancer patients to prevent chemo-induced neuropathy.
• 8:56
  SPEAKER_00: The safest approach, if you are on chemotherapy, discuss ALA use with your oncologist.
• 9:02
  SPEAKER_00: They may allow it for side effect relief at trusted doses.
• 9:06
  SPEAKER_00: Or advise caution.
• 9:07
  SPEAKER_00: Beyond chemo, ALA can have mild blood thinning effects in lab studies, so it might boost bleeding risk if taken with anticoagulant or antiplatelet drugs.
• 9:17
  SPEAKER_00: Again, solid evidence in humans is lacking, but if you're on a blood thinner, like warfarin or aspirin, mention ALA to your doctor to decide if any extra monitoring is needed.
• 9:27
  SPEAKER_00: Forms, dosing, and bioavailability.
• 9:30
  SPEAKER_00: ALA supplements come in different forms.
• 9:32
  SPEAKER_00: The natural form of ALA in the body is the RNantiomer, RAA image SALA form exists only in synthetic mixtures.
• 9:40
  SPEAKER_00: Most over-the-counter supplements use a racemic mixture, 50% RALA plus 50% SALA.
• 9:46
  SPEAKER_00: Some high-end products use pure RALA often as a sodium salt for stability, which is better.
• 9:52
  SPEAKER_00: Surprisingly, pure RALA is actually less stable.
• 9:55
  SPEAKER_00: It tends to form polymers that reduce absorption.
• 9:58
  SPEAKER_00: Studies have shown that having the S form present helps prevent this polymerization, so many experts now favor a high-quality racemic ALA supplement.
• 10:07
  SPEAKER_00: One review noted that the presence of the S enantiomer in the racemic mixture prevents polymerization of RALA, increasing its bioavailability.
• 10:16
  SPEAKER_00: In practical terms, most people do well with standard racemic ALA capsules, 600 to 1200 milligrams total per day.
• 10:23
  SPEAKER_00: Some products use sodium RALA, NRALA, or other formulations to improve stability and absorption.
• 10:31
  SPEAKER_00: Bioavailability.
• 10:32
  SPEAKER_00: ALA is quickly absorbed from the gut, but its bioavailability is somewhat limited.
• 10:37
  SPEAKER_00: It peaks in the blood about 30 to 60 minutes after a dose.
• 10:41
  SPEAKER_00: Crucially, food interferes.
• 10:43
  SPEAKER_00: Taking ALA with a meal can significantly reduce absorption.
• 10:47
  SPEAKER_00: To maximize uptake, ALA should be taken on an empty stomach at least 30 minutes before meals.
• 10:54
  SPEAKER_00: Some studies of specific formulations, like a 600 mg soft gel, confirmed rapid absorption and good bioavailability when taken properly.
• 11:03
  SPEAKER_00: In diabetes studies, doses of 600 to 1200 mg per day are common.
• 11:07
  SPEAKER_00: For glaucoma neuroprotection, research often used 600 mg or higher.
• 11:12
  SPEAKER_00: RALA and racemic ALA appear to have similar safety at these doses.
• 11:17
  SPEAKER_00: If you're new to ALA, it's reasonable to start low, e.g., 300 mg once daily, and increase as tolerated because higher doses, 600 mg, are more likely to show effect.
• 11:29
  SPEAKER_00: Side effects and precautions.
• 11:31
  SPEAKER_00: Overall, ALA is well tolerated.
• 11:34
  SPEAKER_00: Clinical reviews note that side effects are usually mild and occur about as often as with placebo.
• 11:39
  SPEAKER_00: The most commonly reported symptoms are gastrointestinal and skin-related.
• 11:44
  SPEAKER_00: For example, nausea, indigestion, or heartburn can happen, and some people get mild skin rashes or itching.
• 11:51
  SPEAKER_00: In one analysis of trials, about one-third of patients on ALA reported occasional heartburn, and some noted a change in urine odor.
• 11:59
  SPEAKER_00: These effects generally resolve if the dose is lowered or stopped.
• 12:03
  SPEAKER_00: Serious side effects are rare.
• 12:05
  SPEAKER_00: As noted above, the only serious concern from reports is rare autoimmune hypoglycemia in genetically susceptible individuals.
• 12:13
  SPEAKER_00: No increases in blood cancers, organ toxicity, or similar long-term harms have been firmly linked to recommended ALA use.
• 12:21
  SPEAKER_00: Because ALA can lower blood sugar and may lower blood pressure slightly, patients on diabetes or blood pressure medications should monitor for dizziness or hypoglycemia.
• 12:32
  SPEAKER_00: Also, no ALA-containing supplement should be taken without telling your doctor if you are pregnant, breastfeeding, or planning surgery, as its safety in those situations isn't well studied.
• 12:44
  SPEAKER_00: Suggested outcomes for future studies.
• 12:47
  SPEAKER_00: If researchers conduct a clinical trial of ALA in glaucoma or eye health, they should include specific eye-related endpoints.
• 12:54
  SPEAKER_00: Ocular perfusion blood flow.
• 12:57
  SPEAKER_00: Because ALA is thought to improve blood vessel health, measuring eye blood flow is logical.
• 13:01
  SPEAKER_00: Modern technology like OCT angiography can quantify blood flow around the optic nerve, peripipillary region.
• 13:09
  SPEAKER_00: In glaucoma, studies find parapellary vessel density and flow index are significantly lower in patients than healthy eyes.
• 13:16
  SPEAKER_00: A trial could measure these OCTA blood flow indexes before and after ALA, or compare ALA versus placebo to see if perfusion improves.
• 13:25
  SPEAKER_00: Retinal nerve fiberlayer RNFL and optic nerve integrity.
• 13:29
  SPEAKER_00: The thickness of the RNFL on OCT is a standard surrogate for nerve health and glaucoma.
• 13:34
  SPEAKER_00: Animal studies with ALA showed more optic nerve fibers survived.
• 13:38
  SPEAKER_00: So in patients, a key endpoint would be a change in RNFL thickness over time.
• 13:43
  SPEAKER_00: In practice, one could track RNFL thickness or optic nerve OCT measurements and visual field testing.
• 13:50
  SPEAKER_00: If ALA truly protects nerves, treated eyes should show less RNFL thinning and slower visual field loss compared to controls.
• 13:57
  SPEAKER_00: Functional vision tests, visual field sensitivity or contrast sensitivity tests, might also be used, although they can be variable.
• 14:05
  SPEAKER_00: Still, combining structural OCT and functional visual field data would give a full picture of any neuroprotection from ALA.
• 14:14
  SPEAKER_00: In short, future glaucoma studies of ALA should measure ocular blood flow, perfusion, and optic nerve structure, RNFL thickness, as primary outcomes.
• 14:24
  SPEAKER_00: Conclusion: Alpha-Lopoic acid is a promising nutritional neuroprotective agent.
• 14:29
  SPEAKER_00: Its potent antioxidant action can counter oxidative stress, which plays a role in both glaucoma and diabetes complications.
• 14:36
  SPEAKER_00: Research suggests that ALA supplementation boosts antioxidant defenses in the retina and helps preserve retinal ganglion cells in glaucoma models.
• 14:45
  SPEAKER_00: In diabetic patients, ALA modestly improves blood sugar control and has well-documented benefits for diabetic neuropathy.
• 14:53
  SPEAKER_00: For most people, ALA, 600 to 1200 milligrams per day, is safe and causes only mild side effects, nausea or rash.
• 15:00
  SPEAKER_00: However, certain situations deserve caution.
• 15:04
  SPEAKER_00: It may rarely trigger autoimmune hypoglycemia, and it can theoretically interfere with thyroid or chemotherapy drugs.
• 15:13
  SPEAKER_00: Patients on diabetes medications should monitor blood sugar, and those on levothyroxine or chemotherapy should discuss ALA use with their doctors.
• 15:21
  SPEAKER_00: Given the evidence, glaucoma patients, especially those with vascular risk factors and diabetic patients, might consider ALA as part of their supplement regimen after consulting a physician.
• 15:32
  SPEAKER_00: However, we need more clinical trials in humans.
• 15:36
  SPEAKER_00: Any new glaucoma trial of ALA should keep an eye on ocular perfusion, blood flow metrics, and retinal nerve fiber layer thickness as endpoints.
• 15:46
  SPEAKER_00: Such studies will tell us whether this antioxidant can make a real difference in preserving vision.
• 15:52
  SPEAKER_00: All links to sources are available in the text version of this article.
• 15:56
  SPEAKER_00: You can find the full article at VisualFieldTest.com.
• 16:00
  SPEAKER_00: Thanks for listening.
• 16:01
  SPEAKER_00: To check your visual field, click the link at the bottom of this article or visit visualfieldtest.com.