Intravenous administration of ALA at doses of 600 mg/day for three weeks did not result in serious adverse effects when used to treat diabetic peripheral neuropathy. Adverse effects at high dosages include skin conditions, possible hypoglycemia in diabetic patients, and thiamine deficiency. Intravenous ALA is often put into a dextrose solution so that a precipitous drop in blood glucose will not occur.
There are no reports of lipoic acid deficiency, suggesting that humans arc able to synthesize enough for basic enzyme cofactor needs.
LA is found in the mitochondrial cells, normally found in muscle cells. Due to this fact, vegetarians will take in less dietary lipoic acid than meat eaters. Vegetarians who don’t eat green leafy vegetables (another source of LA) arc theoretically at greater risk for deficiency.
ALA seems to live up to its reputation as a superior antiaging antioxidant. Its most promising role is the one it plays in diabetes management and in lessening the symptoms of diabetic neuropathy and glaucoma in particular. Its role in preventing age-related cognitive decline also seems promising, but more human studies arc needed in this regard. The role of alpha lipoic acid in the prevention and management of cardiovascular disease and cancer looks positive so far, but more studies are needed in this regard.
The intravenous dose that seems to be effective for treating diabetic neuropathy is 600 mg per day. Oral dosages of anywhere between 300 mg and 600 mg have been used for reducing neuropathy symptoms. Most supplements of ALA are available in doses of 25-100 mg, with the higher doses being reserved for a specific condition such as diabetes.
The richest sources of lipoic acid arc animal proteins and green leafy vegetables. Liver, heart, and kidney arc particularly high in lipoic acid, because of their high concentration of mitochondrial cells. Green vegetables that have a high concentration of chloroplasts are also rich in LA. Chloroplasts are key spots for energy production in plants, and they require LA for this activity. For this reason, broccoli, spinach, and other green leafy vegetables like collard greens, bok choy, or chard arc good food sources of LA.
There is a lot of hype around using alpha lipoic acid as a general antiaging supplement. It is probably one of the more popular antioxidant supplements around and is sold as a single supplement or as part of a complex (often together with vitamin C, vitamin E, and acctyl-L-carnitine). For 20 years, alpha lipoic acid supplements have been used to treat diabetes, cancer, neurological problems, vascular disease, cataracts and glaucoma.
ALA for Diabetes Management
The best-documented application for ALA in diabetes is its ability to help with symptoms of diabetic neuropathy.
ALA may have a more direct effect on diabetes too, by simply lowering blood sugar levels, through an increase in insulin sensitivity and a decrease in gluconeogenesis.
ALA works against insulin resistance by increasing the permeability of cell membranes, which is decreased by hyperglycemia. It also prevents the uptake of glucose. In human studies, oral supplementation with alpha lipoic acid has proven only marginally effective in helping to improve glycemic control, but intravenous infusions do help affect insulin-mediated glucose disposal and lower blood sugar. A review study on the benefits of oral ALA in diabetes management supports the use of LA for glycemic control, and as a general antioxidant, but states that the major benefit of ALA supplementation is in patients with diabetic neuropathy. ALA has been used in Germany for more than 30 years as a treatment for diabetic neuropathy. Many studies have been published in this regard and the beneficial effects have been reiterated time and again. Diabetic neuropathy is a painful and debilitating consequence of diabetes and is defined as deranged function and structure of peripheral motor, sensory, and autonomic neurons, involving either the entire neuron or selected levels.
A large, randomized, placebo-controlled, multicenter, double-blind study involving 328 patients with type 2 diabetes revealed that intravenous Lipoic acid significantly improved symptoms of diabetic neuropathy, including sensations of burning, tingling, itching, and pain. The same researchers later found that five weeks of oral supplementation with lipoic acid significantly improved the stabbing pain, burning pain, and numbness of the feet in patients suffering from diabetic neuropathy, with the dose-effectiveness range being 600-l,800 mg of lipoic acid dosed orally per day. According to the authors, while some studies on orally administered alpha lipoic acid had suggested a reduction in neuropathic deficits associated with neuropathy, its effects on improving sensory symptoms is still in doubt.
ALA Prevents Cognitive Decline
ALA may play a role in the prevention of brain aging. Rat studies have pointed to an antioxidant protective effect of ALA on cortical neurons. ALA protects against Alzheimer’s by preventing the oxidative stress and energy depletion caused by deranged glucose metabolism and free radical production. In this study 600 mg of ALA was given daily to nine patients with Alzheimer’s and related dementias for roughly a year and led to some stabilization of cognitive function.
Studies using a combination of ALA and acetyl-L-carnitine show even more promise for prevention of age-related brain aging. A study showed that an antioxidant concoction including ALA and acctyl-L-carnitinr reduced reactive oxygen species in normal mice by 57 percent and prevented the increase in reactive oxygen species normally observed in mice lacking murine ApoE (a gene that influences Alzheimer’s disease).
A review of studies on L-carnitine and alpha lipoic acid between 1966 and 2007 showed that L-carnitine and alpha lipoic acid arc pleiotropic agents capable of offering neuroprotective and possibly cognitive-enhancing effects for neuropsychiatry disorders in which cognitive deficits arc an integral feature.
ALA for Cardiovascular Disease
Atherosclerosis (hardening of the arteries), caused by high LDL cholesterol levels and a variety of other factors, is America’s biggest killer. ALA may play a role in the fight against cardiovascular disease by inhibiting monocyte adhesion and endothelial activation, which leads to oxidative stress and atherosclerosis due to oxidative stress. In addition, ALA may help prevent hypertension, another risk factor for atherosclerosis and heart disease, through its ability to raise glutathione levels and suppress endothelin-1 (a substance produced in blood vessels that regulates their tone). ALA has the potential to improve endothelial function and is part of one of the most powerful biological antioxidant systems; however, there is no consensus on dosage, dose frequency, form of administration, and/or preferred form of ALA.
ALA and Cancer
The intracellular redox state plays an important role in controlling inflammation, a process that can lead to tumor progression. ALA has been hypothesized to be able to restore redox control and therefore inhibit inflammation and tumor progression. One study showed that ALA is toxic to leukemia cells, inhibits proliferation of mitogcn-stimulated human peripheral blood lymphocytes, and increases interleukin-2. Another study showed that ALA is able to selectively inhibit the growth of tumorigenic as compared to nontumorigenic ovarian surface epithelial cells and may play a role in ovarian cancer prevention and management. It has also been shown that ALA can effectively induce apoptosis (cell death) in human colon cancer cells by a mechanism that is initiated by an increased uptake of oxidizable substrates into mitochondria.
ALA Offers Promise in Supporting Optimal Visual Health
Lipoic acid has been shown to offer protection against cataract formation in experimental animal models. Scientists believe that lipoic acid may confer this benefit by increasing levels of essential endogenous antioxidant enzymes such as glutathione peroxidase.
Another causc of vision loss, common in diabetes, is glaucoma. A study in patients with open-angle glaucoma found that visual function and other measures of glaucoma were improved in a group that received either 75 mg of lipoic acid daily for two months or 150 mg of lipoic acid daily for one month, compared with a control group that received 110 lipoic acid. A recent review of natural therapies for cataracts and glaucoma lists ALA as a potential therapy, but no conclusive evidence on effectiveness and recommended dosages can be given yet.
ALA May Protect the Liver
ALA has various applications when it comes to liver function. In animal studies, lipoic acid has been shown to safeguard the liver against the effects of cadmium exposure (an environmental toxin that is also found in cigarette smoke).
Fatty liver disease, a common symptom of metabolic diseases and diabetes, is associated with high levels of circulating l’ats, callcd triglycerides, in the blood. High triglycerides arc also linked to an increased diabetes and heart disease risk. In animal studies ALA has been shown to improve hypertriglyceridemia by stimulating tria-cylglycerol clearance and down regulating liver triacylglycerol secretion.
Another mechanism of action by which ALA lowers triglyceride levels and decreases hepatic lipogenesis (fat production by the liver) is through its influence on adenosine monophosphate (AMP)-activated protein kinase (AMPK), a major regulator of energy metabolism. This effect on AMPK also results in an increase in insulin sensitivity.
ALA for Healthy Skin
ALA may improve the health of the skin and is a commonly used ingredient in topical skin care products. A study of 33 women with an average age of 54 years found that twice-daily application of a cream containing 5 percent lipoic acid for three months reduced the roughness of the skin and decreased the appearance of photoaging, compared with a control cream.
One antioxidant getting a lot of attention on the free radical fighting scene is alpha lipoic acid. It is produced in the body as lipoic acid (LA), also sometimes called thioctic acid. It is absorbed from certain foods that we cat, but the body produces its own LA for metabolic use. LA plays a role in the Krebs cycle and cellular metabolism of carbohydrates and fats. In supplemental form, LA is known as alpha lipoic acid (ALA). ALA is not quite a vitamin and not quite a fatty acid, although it exhibits properties of each. Unlike other antioxidants, alpha lipoic acid is both water and fat soluble, enabling it to work throughout the body. As an antioxidant supplement, ALA neutralizes hydroxyl radicals and singlet oxygen and can also help regenerate oxidized vitamin C and vitamin E as well as glutathione and coenzyme Q10.
In general, 5-HTP is probably sale and effective for minor to moderate depression. It is not without risk, and it is not definitively effective. Bearing in mind the risk, it is reasonable for people to try it for depression. Even though it is a supplement, consulting a physician while taking the medication is still a good idea. A physician can make sure there arc no other medicines being taken that might contribute to the serotonin syndrome.
There is less research available about other uses. 5-HTP is probably sale and somewhat effective for anxiety and chronic pain conditions including headaches and fibromyalgia.
It is reasonable for people with anxiety or pain to try 5-HTP, especially if standard medical treatment has not worked for them.
Most people who cannot tolerate 5-HTP discontinue it because of nausea or other gastrointestinal symptoms.
It is known that 5-HTP frequently causcs gastrointestinal symptoms including heartburn and nausea, vomiting, and diarrhea. These symptoms may be from conversion of 5-HTP to serotonin in the intestinal tract. Other side effects have been reported, including headache, difficulty sleeping, and palpitations. Starting with a low dose and slowly increasing it may decrease these side effects.
If carbidopa is given with 5-HTP and serotonin is not made in the intestinal tract, these side effects may be minimized. This treatment is rarely recommended and quite controversial. A select few feel that the amount of 5-HTP required to treat depression without carbidopa is so high that it is very likely to cause intolerable side effects.
The eosinophilia-myalgia syndrome is still a concern. Although 5-HTP probably does not causc the syndrome, it is a possibility. It needs to be recognized quickly and the use of the supplement stopped. The hallmarks of the syndrome arc muscle pain (myalgia), spasm and later weakness, and an elevated number of eosinophils in the blood (eosinophilia). There are often skin lesions and swelling of the extremities and face. There can be lung and nerve problems. Many of the symptoms persist for years.
In order to avoid the serotonin syndrome, people who are taking SSRIs or have recently taken them may want to be careful when taking 5-HTP. They should be mindful of the symptoms of serotonin syndrome, including high blood pressure, elevated temperature, flushing, sweating, dizziness, muscle jerks, and disorientation. These symptoms usually come on within hours of too high a serotonin elevation. The syndrome resolves in 24 hours in approximately 70 percent of cases. It is usually not serious, although there have been deaths. Now that the symptoms of this syndrome arc known, it is easier to catch it early and prevent any complications.
While SSRIs affect serotonin levels the most, other antidepressants can also raise serotonin levels, as can certain other medications including some used for migraine headaches. Anyone who is taking a prescription antidepressant or any other medication that raises serotonin should talk to his or her doctor before adding 5-HPT. If unsure about a particular medicine, it is safest to find out if it increases serotonin by asking a doctor or pharmacist.
Any supplement or medicine that can treat depression has the potential for triggering mania in bipolar patients, patients with both mania and depression. It is very difficult to treat bipolar illness; it should be done by or in conjunction with a physician who has experience treating patients with the disease.