Alpha Lipoic Acid (ALA), also known as thioctic acid (TA), has gain substantial popularity over the years as a nutritional supplement.

ALA is a natural occurring compound that exerts antioxidant activity in the body. We can also source it from various vegetables such as spinach, broccoli, yams, potatoes, yeast, tomatoes, brussels sprouts, carrots, beets, and rice bran. Red meats were also found to contain some amounts of ALA. (1)

Experimental studies on ALA have investigated its potential therapeutic effects on diabetes, obesity, cardiovascular diseases, non-alcoholic fatty liver disease, blood pressure, other types of cancer. (2)

For this article, we’ll go over alpha-lipoic acid effects on diabetes and the effects on blood sugar.

Clinical Studies

Before we dive into the clinical trials of ALA, let’s get to know more about this antioxidant compound.

Alpha-lipoic acid is synthesized through the mitochondria where enzymatic complexes engage in cellular energy production. ALA’s operates as restoring the body’s antioxidant system, generates antioxidants for cells accessibility, and removes heavy metals in the bloodstream. It also has important roles in glucose metabolism, scavenge free radicals, remediate oxidative stress, and stimulate key cellular signaling. It was noted to induce insulin, anti-inflammatory, and AMPK responses all of which translates to increase insulin sensitivity, relieve inflamed responses, and regulate energy production. (3)

Now that we have an idea of ALA antioxidant function let’s shift our focus its effectiveness on glucose and diabetes.

In 2019, research has estimated that 463 million adults are diagnosed with diabetes. Debilitating symptoms symptoms can range from insulin resistance, hyperglycemia, cardiovascular disease, kidney disease, nerve damage, and vision impairment. (4)

1. To examine ALA on diabetes, researchers randomized one hundred and five diabetic patients and some received a capsule mixture of 600mg of ALA, 165mg of L-carnosine, 7.5mg of zinc, and the remainder of B vitamins while others received a placebo. They evaluated measures such as body mass index, fasting plasma glucose, after-meal glucose, HbA1c, lipid markers, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA). SOD and GSH-Px are antioxidant enzymes that battles reactive oxygen species to prevent cellular damages. MDA is a biomarker to measure oxidative stress in cells.

At the end of three months, researchers documented reductions from baseline measures of the ALA group. They notice decreased levels in fasting glucose, post-meal glucose, HbA1c, LDL, and triglycerides. Antioxidant markers such as SOD and GSH-Px, had notably increases while MDA displayed decreases compared to the placebo group. (5) 

Based on this study, alpha-lipoic acid was able to induce positive reductions in glycemic and lipid measures. It was also noted to increase antioxidants as well as alleviate oxidative stress marker, malondialdehyde. This suggests ALA to be a potent antioxidant supplement targeting multiple cellular regions.

We must also consider the ingredient mixture supplemented with ALA may play a role in increasing its effectiveness. Ultimately, these effects were able to ameliorate free radicals and other oxidative stressors which reduce glucose levels and lipid markers. In conclusion, ALA was confirmed to induce therapeutic benefits in supporting glycemic control as well as improve antioxidant properties in diabetics.

"There was a reduction of FPG, PPG, and HbA_1c with the food supplement containing α-lipoic acid compared with a baseline, and with the placebo. Concerning lipid profile, we observed a reduction of LDL-C, and Tg with the food supplement, compared with both the baseline, and the placebo. There was a reduction of Hs-CRP with the food supplement containing α-lipoic acid, both compared with the baseline and the placebo. An increase of SOD, and GSH-Px, and a decrease of MDA were reached by the food supplement containing α-lipoic acid, both compared with the baseline and the placebo. We can conclude that the food supplement containing α-lipoic acid, L-carnosin, zinc, and vitamins of group B improved glycemic control, lipid profile, and anti-oxidative stress markers." (5) 

2.  Studies have shown that diabetes exhibit formation of free radicals, decrease antioxidant supply, and induce oxidative damages in the cell’s functionality. When blood glucose increases to high levels it begins to produce reactive oxygen species (ROS) which results in an overproduction of oxygenize chemicals. This creates oxidative stress in the mitochondria thus reducing cellular performance. This process can lead to detrimental complications such as beta cell destruction, insulin resistance, nerve damage, and cardiovascular issues. One of the issues associated with diabetes is diabetic neuropathy.

Neuropathy is a result of nerve damages which usually causes weakness, numbness and pain mainly in the hands and feet.

A small study was conducted on patients with diabetic neuropathy. After the subjects were given ALA researchers observed increased levels of nitrates and nitrites. Researchers theorized the increase of nitric oxide markers such as nitrates and nitrites may lead to an increase circulation to the neurons. (6)

In a lab study, researchers tested ALA’s effects on brain and sciatic tissues and revealed that it was able to reduce high glucose induced-lipid peroxidation in both tissues. Lipid peroxidation is another oxidative breakdown in phospholipids that occurs in various cellular membranes. This can lead to cytotoxicity in organs such as liver, kidneys and brain. (7)

Researchers confirmed ALA’s lipid peroxidation lowering effect in diabetic patients. Ten diabetic patients were administered with 600mg of ALA for seventy days. Researchers observed reductions in lipid peroxidation and increase enzymatic activity in the brain. (8)

Based on these findings, it does appear that ALA was confirmed to support diabetic neuropathy by reducing oxidative stress in brain and spinal tissues as well as increase fuel circulation in the neurons. In some case, ALA does support nerve damage in a modest way. Other studies have confirmed ALA to significantly alleviate other neuropathy complications from other patients. In conclusion, ALA was shown to support diabetic neuropathy based on these clinical trials. More studies are needed to assess the ALA’s consistent claims for a more confident validation.

"Given the growing evidence for increased oxidative stress and inflammatory pathways activated in diabetes, therapeutic paradigms may have to shift to target these processes through the use of compounds such as ALA. So far, the strongest evidence for the clinical use of ALA is from double blind, placebo controlled trials showing that LA administration significantly ameliorates polyneuropathies associated with diabetes." (8)

3. Another clinical trial tested the effects of ALA against insulin sensitivity on diabetic patients. The study aimed to test twelve patients with type II diabetes. They received 600mg of ALA administered twice a day for four weeks. (9)

Researchers measured the patients’ insulin resistance and sensitivity at the end of the study. To assess the values, researchers documented their insulin resistance by their glucose disposal rate. The higher their glucose disposal rate the less risk of developing insulin resistance. (10)

Positively, the effects of ALA were seen to increase their glucose disposal rate by 85% which also led to a reduction in patients’ insulin resistance. For the patient’s insulin sensitivity index, ALA did manage to increase their insulin index; but in comparison with the control group the difference was not that significant. (11)

Based on this study, the ALA treatment on type II diabetic patients showed modest improvements on their insulin sensitivity parameters. Although the results were not as drastic, ALA was able to display sensitizing activity. In conclusion, alpha-lipoic acid is seen to increase sensitivity as well as improve insulin resistance on type II diabetics to some degree.

"short-term oral alpha-lipoic acid treatment increases peripheral insulin sensitivity in patients with type 2 diabetes mellitus. " (11)

4. Another study was conducted to test alpha-lipoic acid on twenty type II diabetic patients for repeated treatment. The aim was to repeat ALA’s effects on patients’ glucose disposal. For ten days the participants received 500mg of ALA through an infusion therapy which was intravenously entered their bloodstream. Researchers recorded an increase in insulin-stimulated glucose disposal by 30%. Other measures such as fasting plasma glucose or fasting insulin did exhibit notable changes during the trial. But for the short ten-day period, ALA was seen to improve glucose disposal in the patients’ skeletal muscles. (12)

Glucose disposal is the process of insulin pulling glucose from the bloodstream and redirecting them into muscle tissues. This process improves insulin’s activity by reducing high levels of glucose in the body and disposing them into the muscle instead of fat.

In conclusion, this study confirmed ALA potential mechanisms of inducing insulin-stimulated glucose disposal in a short period of time. This serves as a potential therapeutic action to support unhealthy levels of blood sugar.

5. In a mice study, researchers conducted research of the effects of alpha-lipoic acid on type II diabetic mice. They selected twenty-nine mice subjects divided into three groups: one group given the ALA treatment, a non-diabetic control group, and diabetic control group. The diabetic control group were treated with a low dose of streptozotocin which is a compound that induces diabetic complications. The duration of the test stood for four weeks and blood samples were taken immediately. Researchers measured the mice’s body weight, glucose, triglycerides, total cholesterol, LDL-cholesterol and HDL-cholesterol. (13)

For the ALA-treated group, their body weight displayed no significant difference when compared with the diabetic control group. Although, both groups showed a greater reduction in body weight compared to the non-diabetic control group. (14)

A high fat diet was fed to both diabetic and ALA-treated rats. While the non-diabetic group were fed with a standard diet. The diabetic control group had glucose levels drastically higher compared to both groups. The group that received ALA experienced 2.4 fold decrease in their blood glucose levels compared with the diabetic group. This confirms ALA’s hypoglycemic effect on mice that were fed with a high fat diet. (15)

As for lipid measures such as triglycerides, total cholesterol, and LDL-cholesterol were all observed to have considerable increases in the diabetic group. Inversely, the ALA-treated group exhibited positive reductions in all three measures by 1.2-fold, 1.5-fold, and 0.9-fold, respectively. Surprisingly, ALA also demonstrated increases levels of HDL-cholesterol by 1.2-fold. Coronary values were also measured and discovered that ALA-treated mice presented major decreases in risk of atherosclerosis development. It does seem ALA is able to improve various cholesterol markers in mice thus suggesting ALA’s therapeutic potential in cardiovascular disease. (16)

The supporting evidence does confirm ALA’s metabolic and cardiovascular activity based on the results above. ALA’s mechanisms on glucose seem to be directed to its insulin signaling activity and activation of AMPK which can led to hypoglycemic and insulin sensitivity effects. Especially when mice are fed a high fat diet their glucose can spike to high levels in which ALA is capable of remediating this effect.

ALA’s also exhibited cardiovascular support by reducing various lipid markers such as triglycerides, total cholesterol, and LDL. Interestingly, ALA increased HDL levels suggesting substantial improvement in mice’s lipid profile.

Lastly, ALA demonstrated signs of lessening the risk of atherosclerotic damages. ALA effectively decreased diabetic symptoms as well as their cardiovascular health. These findings do seem to be validate ALA benefits on glycemic index and cholesterol profile. Be mindful these results were attained through experimentation on mice. Other studies do confirm similar findings on humans but additional concrete testing is needed to verify ALA’s effect confidently.

"Furthermore, ALA treatment significantly increased the serum HDL‐cholesterol levels and tended to inhibit diabetes‐induced weight reduction. Mathematical computational analysis revealed that ALA also significantly improved insulin sensitivity and reduced the risk of atherosclerotic lesions and coronary atherogenesis. This study provides scientific evidence to substantiate the use of ALA to mitigate the glucose and lipid abnormality in metabolic syndrome and T2D. " (16)

6. A similar animal study investigated ALA’s effect on mice fed with a high fat diet. For a ten-week period, the mice experienced increased levels of oxidative stress, prevented glucose uptake, decrease cellular energy content, and lowered immunocyte production. (17)

The treatment combined both ALA and N-acetyl-L-cysteine. Researchers discovered all of these measures were ameliorated. The treatment promoted antioxidant and anti-inflammatory activity by stimulating Nrf2 expression. Nrf2, transcription factor located in our genes, is responsible for inducing oxidative protection and reduce inflammatory damages in the cells. (18)

In conclusion, the study conducted on high fat diet mice exhibited decreased levels of inflammatory responses and alleviated glucose impairment due to ALA’s antioxidant and inflammatory signaling. By reducing oxidative stress in immunocytes this could lead improvements on mice’s glucose levels, free radicals, regulate ATP production and proliferate T-cell activity. Although this was confirmed on a mice study, more clinical trials are needed to validate these claims.

"Results showed that 10-week HFD increased intracellular reactive oxygen species (ROS) production, induced oxidative stress state formation, inhibited glucose uptake, decreased ATP concentration, reduced proliferative rate, and dampened IL-2 production of T cells of mice. Administration of LA significantly alleviated these changes induced by HFD. These findings reveal that oxidative stress of T cells caused by HFD may be a key factor leading to glucose metabolism reduction and proliferative capability and function impairment of T cells. LA, as a potent agonist, could promote Nrf2 nuclear translocation and up-regulate expression of Nrf2 target genes (Ho-1 and Prdx1), which can eliminate excess ROS and restore redox balance of cells. " (18)

7. An in-depth clinical trial investigated the metabolic effects of ALA. Twenty-two patients received an IV-administered ALA solution for twenty-two weeks. Researchers observed improvements in fasting and average blood glucose, insulin sensitivity, LDL, HDL and total cholesterol. They also tracked significant reductions on inflammatory markers such as including tumor necrosis factor (TNF), interleukin-6 (Il-6), 8-isoprostandin, and malondialdehyde (MDA) which are known to be elevated by diabetes. (19)

It does seem ALA was able to induce glycemic improvements, increase insulin sensitivity, support lipid index, and reduce inflammatory markers relating to oxidative damages. For this study, the method of administering ALA seems to be the key factor in achieving the effects. By injecting the solution straight to the patients’ bloodstream appears to have a stronger effect that orally ingesting ALA capsules. Although improbable in most real-life situations, this method helps us understand the mechanisms in which ALA can alleviate diabetic complications.

"ALA significantly reduced each of these markers. In addition, the researchers found a statistical correlation between insulin sensitivity and each individual marker of inflammation and oxidative stress - lending credence to the idea that by reducing oxidative stress and inflammation, ALA can then increase insulin sensitivity and improve blood sugar and lipid control." (19)

8. Several studies have also confirmed ALA’s insulin sensitivity and the effects on glucose control. One study tested seventy-four patients with hyperglycemia with ALA supplementation. They were divided in four groups: placebo, one dosage, two dosages, and three dosages. At the end of the four-week trial, researcher’s observed significant improvements in their insulin sensitivity. But it was also noted there were no considerable differences between the dosage amounts. This study confirms ALA to support patients’ insulin sensitivity through various doses. Even at end of four-week period researchers observed positive outcomes from ALA’s effects. For glucose and insulin control, ALA may possess therapeutic mechanisms for patients with hyperglycemia. (20)

"ALA treatment led to significant improvement in MCR, though there was no significant difference between doses." (20)

9.  To wrap up, ALA’s efforts on glucose support was summed up in a meta-analysis which is an aggregate total of multiple reports. The meta-analysis reported five studies with one-hundred and forty human participants. ALA demonstrated significant reductions on the patients’ fasting blood glucose in those that had a stroke. As for cholesterol profile, multiple findings reported no significant effect on triglycerides, total cholesterol, LDL-cholesterol and HDL-cholesterol. (21)

The observations across all studies seem to report ALA’s effectiveness on lowering fasting glucose. But unfortunately, there appears to be conflicting findings as ALA supplementation was not capable of improving lipid markers mention above. It seems that ALA may have inconsistent yields which could mean the results vary per each patient. But nonetheless, this meta-analysis validated ALA’s support on hypoglycemic effects.  

TAKEAWAY: Based on the studies above, alpha-lipoic acid was validated to help blood sugar levels by increasing insulin sensitivity, glucose disposal, and improve various glycemic indexes. ALA’s antioxidant nature also alleviated diabetic neuropathy by restoring neuron circulation in the brain.

Several studies also reported ALA to increase enzymatic activity by boosting other antioxidant compounds; which can ameliorate oxidative and inflammatory stressors elevated by diabetes.

This natural remedy seems to display promising evidence to support diabetic complications by reducing high glucose levels and alleviate insulin resistance.

Due to numerous clinical trials, results present ALA as a powerful antioxidant treating hyperglycemia at dosages from 300-1200mg. Majority of the studies have yielded very similar results regarding blood sugar and lipid support while others have conflicting verdicts on ALA’s lipid effects. This shows that ALA’s benefits may not work in most cases but in some it can vary from person to person. Overall, supplementing ALA was proven to have strong therapeutic effects on glucose control. As for its future potential, more research is required to solidify ALA as a potential medication for diabetic symptoms.