A Real Pain

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Post by Neil McKellar-Stewart28 Nov 2011

PERIPHERAL NEUROPATHY IS A COMMON COMPLAINT OF MANY PEOPLE LIVING WITH HIV.

The symptoms vary but usually consist of unpleasant ‘stabbing’ pains or tingling, burning, numbness or cramps in the hands and feet. It can make walking or placing weight on your feet quite painful. And it can have a huge negative impact on your quality of life.

Those of us who have lived with HIV through the 1990s remember it as one of the more unpleasant side effects of the older nucleoside reverse transcriptase inhibitors (NRTIs) like d4T (stavudine) and ddI (didanosine), both of which are now rarely used in Australia.

But HIV itself can also cause peripheral neuropathy (PN). Even people on effective treatment with undetectable viral loads can still experience nerve tissue damage. The cause is not fully known but it may relate to macrophage cells in the nervous system and associated small blood vessels being infected with HIV. This might then stimulate the production of chemicals which causes inflammation that damages nerve fibres, particularly the longer ones in the feet and arms.

The other factors associated with PN are increasing age, height, high intakes of alcohol and the extent to which your immune system was damaged before starting treatment (sometimes measured by your lowest CD4 count or ‘nadir’).

STUDIES + LINKS

A recent study called ALLRT (AIDS Clinical Trials Group Longitudinal Linked Randomized Trials) followed more than 2000 PLHIV for seven years after they had started on treatment. It revealed that 30% of them had some HIV-associated peripheral nerve damage and up to 20% of them experienced some pain in their feet. Nerve function was measured by assessing the signs (vibration sensation at the feet and ankle reflexes) and symptoms (pain, ‘pins and needles’ sensation and numbness). All these people were being effectively treated and their median CD4 cell count was around 500.

Another study of 436 PLHIV in California (between 2000 and 2008) found some interesting associations between PN and levels of triglycerides (one of the lipids or ‘fats’ we regularly monitor in blood tests). In this study, almost everyone had an undetectable viral load and their current median CD4 cell count was around 460.

Amongst them, nearly 30% had some signs of PN. They may not have experienced pain or other symptoms, but they were judged to have nerve damage by signs such as reduced vibration or sharp sensation and reduced ankle reflexes. Like the larger ALLRT study, the same factors (age, height, nadir CD4) were also associated with PN. And there was some suggestion that those who took a protease inhibitor showed higher rates.

The important finding in this study was that people with higher triglycerides were also more likely to have PN.

People who had levels in the range of 1.6 to 2.75mmol/L were one and a half times more likely of having PN and the probability was 2.6 times higher for those with triglyceride levels greater than 2.75 (compared to people with levels below 1.6).

The National Heart Foundation of Australia advises that triglyceride levels greater than 2.0 bring increased risk of heart and other diseases. A lot of PLHIV have trig levels higher than this, and it is often combined with lower levels of HDL or ‘good’cholesterol.

It is thought that high levels of triglycerides alter the way mitochondria function and increase the release of chemicals which can damage nerve fibres.

Triglycerides also affect blood flow in very small blood vessels which may also result in nerve damage.

In diabetics there is accumulating evidence that oxidative stress (through production of free radicals) is part of diabetic neuropathy.

Diabetics often have elevated triglycerides which contribute to their peripheral neuropathy. It is thought that damage to the blood vessels supplying oxygen to nerve tissues starves them of sufficient oxygen and thus damages them. Antioxidant treatment with Alpha Lipoic Acid has been shown to prevent these abnormalities.

So, both HIV itself and high levels of triglycerides are factors linked to inflammation in the peripheral nerves and associated blood vessels.

Clearly, reducing the inflammation associated with HIV is the first step to minimising the risk of acquiring peripheral neuropathy. Treating HIV itself will reduce this inflammation, and so, consistent with Australian Antiretroviral Guidelines, startingHAART should be considered in all PLHIV when their CD4 counts fall to less than 500, and definitely started by the time CD4 count reaches 350. Using dietary supplements of 3 to 5 grams per day of omega-3 fatty acids (fish oils) have been shown to be highly effective in reducing triglyceride levels. As have drug-based therapies using niacin and/or fibrates.

ALPHA LIPOIC ACID

Alpha Lipoic Acid (ALA or thioctic acid as it is sometimes known) is a naturally occurring compound that is metabolised in the mitochondria of human cells and which has a critical role in the production of energy within cells. Small amounts are absorbed from dietary sources – including muscle meats, heart, liver and kidney – however, it is in the form of dietary supplements that it has been most studied.

ALA is a potent biological antioxidant, a detoxification agent, and has been used for over 30 years in Europe to treat neuropathy in diabetics; it has also been used to improve age-related cardiovascular, cognitive and
neuromuscular health conditions, and plays a role in moderating inflammation.

ALA promotes the removal of free radicals (an excess of which contributes to oxidative stress) and increases levels of other natural antioxidants such as glutathione and vitamins A and C.

Two recent trials of the use of ALA in diabetic neuropathy have produced evidence that it reduces some of the symptoms of PN.

The NATHAN 1 randomised control trial was conducted over 4 years and involved 460 people who had diabetesand mild to moderate PN. ALA (taken orally) at doses of 600mg daily significantly improved the PN over that time.

In the SYDNEY 2 randomised control trial in 138 people with diabetic PN, it was found that over a short period (five weeks) that oral ALA 600mg/day improved neuropathy symptoms, including stabbing and burning pain, and reduced self-assessed pain levels. In both these trials the side effects were minimal and ALA seemed well tolerated.

In a German study of diabetics who had been successfully managing their PN and its pain with ALA, it was found that discontinuing treatment with ALA led to rapid increases in nerve pain (within as little as two weeks). A group of patients who switched to drug-based pain relief had poorer pain relief and more side effects.

In a small study of people at risk of diabetes (they had impaired fasting glucose) who received 600mg of ALA a day over a period of three weeks, it was found that ALA improved the function of blood vessels so that they were able to expand (dilate) and provide more oxygen to tissue. ALA reduced oxidative stress by reducing levels of free radicals and levels of markers of inflammation. It also reduced trigs. Some studies have found that ALA has been effective in reducing high blood pressure, perhaps because it stimulates production of chemicals that assist blood vessels to expand (dilate and reduce pressure) and because it inhibits chemicals which constrict blood flow through the kidneys.

Recent reviews also suggest that ALA has a role in reducing inflammation associated with multiple sclerosis, Parkinson’s and Alzheimer’s diseases. Some animal studies have shown it may have a role in improving learning and memory, and reducing mental decline (cognitive impairment); however, the only trial of ALA in people with HIV produced inconclusive results.

For some PLHIV it may be useful to improve PN and reduce disease associated with elevated trigs and blood glucose.

HOW SAFE AND HOW MUCH?

Extensive research has shown that Alpha Lipoic Acid as a dietary supplement is safe; however, no upper level of consumption has been established. Doses of 600 to 800mg/day are judged to be safe and effective in reducing oxidative stress.

ALA in dietary sources such as meat and liver is bound to proteins that assist its absorption. The ALA in supplements is not bound to proteins and competes with proteins to be absorbed; it is therefore recommended that ALA be taken away from mealtimes when it will be more readily absorbed.

As with all dietary supplements and complementary therapies, it is strongly recommended that you check with your doctor before you start taking them as they may interact with other medications you are on or otherwise affect your medical care.

You can purchase Alpha Lipoic Acid online from a number of nutraceutical companies. Some AIDS Councils may make it available through their vitamins services. The ACON Vitamin Service in Sydney currently has a supply of ALA (300ml 60 tablets for $16) but remember, they require a letter from your doctor or other healthcare provider.

References

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Evans SR, Ellis RJ, Chen H, et al. (2011). Peripheral neuropathy in HIV: prevalence and risk factors, AIDS, 24;25(7): 919-28.

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Jariwalla RJ, Lalezari J, Cenko D, et al (2008). Restoration of blood total glutathione status and lymphocyte function following alpha-lipoic acid supplementation in patients with HIV infection. J Altern Complement Med, 14(2): 139-46.

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