Neuropathy pain and HIV: supplement recommendations

You may have read reports in late February 2012 about the FDA’s skeptic ism about a patch called Qutenza, which had been tested for relief of neuropathy pain in people with HIV. Following a meeting to review the evidence, an FDA panel concluded that Qutenza, whose active ingredient is a synthetic form of capsaicin (the compound that makes chili peppers hot) was not effective for HIV-related neuropathy pain.

The FDA’s finding on Qutenza reminds us again that neuropathy (generally, pain or tingling in the extremities) continues to be one of the most troublesome effects of HIV/AIDS and/or its treatment—and one of the most difficult to manage. According to a survey report in 2010, for example, more than one third of those on combination antiretroviral therapy for HIV do experience neuropathy, leading to lower quality of life and often disability. So, it may be worthwhile to repeat some of NYBC’s recommendations on this topic:

Peripheral neuropathy: “nukes” (nucleoside reverse transcriptase inhibitors) such mas ddI (Videx), and d4T (stavudine/ Zerit) – and Indinavir, T20, and even 3TC (Epivir)may all cause this feeling of pins and needles or numbness to toes and fingers. It can travel up the legs and become debilitating. HIV, diabetes, alcohol abuse, and vitamin deficiencies can all be causes of peripheral neuropathy. Supplements that are “good for your nerves” and that have the most robust data include acetylcarnitine (1-3 grams/ day, quite well studied for peripheral neuropathy) and alpha lipoic acid (200-600 mg/day). Other agents that can help are Vitamin B12, biotin, lecithin, magnesium, borage oil, evening primrose oil, choline and inositol.

See the NYBC website for more details about these supplements:
http://nybcsecure.org/

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Supplements for the Brain (and Nerves)

“For Your Peace of Mind…”

Recent research on supplements for memory, cognition and other neurological functions
You may remember (we hope you remember!) the Scarecrow’s petition to the Wizard of Oz for a brain. Be advised–we at NYBC do not stock new brains, so don’t come to us with that request.

However, we do follow the sometimes startling new research on supplements, brain function and related neurological issues. In this department, there’s special cause for concern for people with HIV. According to a Canadian study released in 2010, in a group of 1615 people receiving treatment for HIV during the decade 1998-2008, one fourth had neurological problems, including memory loss, cognitive impairment and peripheral neuropathy. Of course being worried about brain function–and neurological function in general–is not unique to people with HIV. As people age, they are more likely to experience memory loss or forms of dementia such as Alzheimer’s. And the nerve condition called peripheral neuropathy (pain, tingling in the feet and hands) is found not just in people with HIV, but also among the growing population with Type 2 diabetes.

Now, on to what we see as some of the most valuable recent findings about supplements and brain or neurological function:

B vitamins can be considered a foundation because they are needed in so many processes essential to the brain’s operation, from energy supply and healthy blood flow, to the formation of neurotransmitters (=chemical messengers of neurologic information from one cell to another). Furthermore, there is evidence that several groups of people, including those over 60 and those with HIV, have a greater risk for Vitamin B deficiencies. So supplementing with a B complex vitamin is a sensible start to cognitive health. More specifically, there is good research linking deficiency of vitamins B12 and B6 to mood disorders like depression—and depression earlier in life is associated with higher risk of dementia in later life. Last, there is also some evidence that B vitamins may reduce stroke risk in older people.

Omega-3 fatty acids (fish oil) support cognitive health in a variety of ways. In 2008, UCLA researchers reported on a lab study showing that the omega-3 fatty acid DHA, together with exercise, improved cognitive function. This caught our attention, because there is wide agreement that regular exercise strongly supports brain function as we age, and here the suggestion is that omega-3 fatty acids multiply that known benefit. A diet rich in omega-3 fatty acids/fish oil has also been linked to lower risk of depression—another plus. And still more: recent research found that omega-3 fatty acids block the development of retinopathy, a chief cause of blindness as we age. (The retina of the eye is actually part of the brain–it is full of nerve cells essential for vision.) All in all, the neurological benefits of omega-3 fatty acids seem both wide-ranging and quite convincing, so it’s high on our recommended list.

The amino acid acetylcarnitine has shown benefit for brain function in a number of studies with humans. In the last decade, acetylcarnitine has also been investigated for peripheral neuropathy in people with HIV. (Some recommend using it with evening primrose oil and Vitamin C.) A 2008 study found that acetylcarnitine influences a chemical process in the brain that triggers Alzheimer’s, so researchers are continuing to puzzle out how this supplement produces its neurological benefits.

Antioxidants. There’s much suggestive research about how antioxidants counter destructive oxidative processes in the brain, thus blocking memory loss and cognitive decline. For example, a 2003 report found that the antioxidant combination alpha lipoic acid and NAC reversed memory loss in aged laboratory mice. And there’s also been a lot of attention to the combination acetylcarnitine and alpha lipoic acid for memory impairment. Furthermore, other antioxidants such as curcumin are under study for their potential to fight the processes that lead to declining brain function.

Acetylcholine. The first neurotransmitter to be identified, acetylcholine is closely associated with memory, with lower levels linked to memory loss. NYBC currently stocks two combination supplements that support acetylcholine levels in the brain, while also providing other nutrients for neurological function: Neuro Optimizer (Jarrow), which includes acetylcholine enhancers, acetylcarnitine, and alpha lipoic acid; and Think Clearly (SuperNutrition), which includes B vitamins, as well as acetylcholine enhancers and a botanical traditionally used for cognitive support, ginkgo biloba.

Resveratrol. In the past decade, there has been intense scientific interest in this compound, most famously found in red wine. While some research ventures have hoped to find in resveratrol a life-extending supplement (a capacity demonstrated in animal studies), others have focused on its therapeutic value for conditions like diabetes or cognitive decline. For example, Cornell researchers reported in 2009 that resveratrol reduced the kind of plaque formation in animal brains that causes Alzheimer’s. And a year later another lab investigation, this one at Johns Hopkins, found that a moderate dose of the compound protected animal brains from stroke damage.

Ginkgo biloba, a botanical derived from Earth’s most ancient tree species, has been widely used for cognitive function. In the late 1990s, two reviews of dozens of ginkgo studies concluded that it could improve symptoms of dementia. However, a long-term trial of ginkgo published in the Journal of the American Medical Association in 2008 found that the supplement did not prevent development of dementia in a group of more than 3000 older people who had normal cognitive function at the start of the research. One possible conclusion: ginkgo may help symptoms of cognitive decline, but doesn’t address underlying causes.

NYBC’s RECOMMENDATIONS: A B complex supplement (like Jarrow’s B-right) and fish oil (like Jarrow’s Max DHA) are foundations for maintaining cognitive health, especially important for people with HIV or people over 60. There is some evidence for acetylcarnitine, alpha lipoic and acetylcholine supplementation for memory impairment and possibly for cognitive decline. Acetylcarnitine and other supplements can be used to address peripheral neuropathy. And stay tuned for emerging research on preserving brain function with compounds like resveratrol, NAC and curcumin.

Acetylcarnitine for cardiovascular health

Acetylcarnitine (or acetyl-l-carnitine) has been studied in recent years for its neuroprotective effects. It is the subject, for example, of some good research on peripheral neuropathy (nerve damage leading to tingling, pain in the hands and feet) in people with HIV.

But we were interested to read about a 2009 report on acetylcarnitine used in a pilot study of people with elevated cardiovascular disease risk. The investigation, which involved 24 weeks of oral acetylcarnitine therapy (1 gram daily), found significant improvement in high blood pressure and glucose control among the study subjects. Since these improvements point to a decrease in cardiovascular disease risk, the investigators suggest that further research be done to see whether long-term acetylcarnitine supplementation can be a good cardioprotective strategy.

Here’s the abstract of the article:

Ameliorating Hypertension and Insulin Resistance in Subjects at Increased Cardiovascular Risk
Effects of Acetyl-L-Carnitine Therapy
Piero Ruggenenti; Dario Cattaneo; Giacomina Loriga; Franca Ledda; Nicola Motterlini; Giulia Gherardi; Silvia Orisio; Giuseppe Remuzzi

From the Unit of Nephrology (P.R., G.R.), Azienda Ospedaliera Ospedali Riuniti, Bergamo, Italy; Clinical Research Center for Rare Diseases “Aldo and Cele Daccò” (P.R., D.C., G.L., F.L., N.M., G.G., S.O., G.R.), Mario Negri Institute for Pharmacological Research, Bergamo, Italy; Institute of Special Medical Pathology (G.L., F.L.), Università degli Studi, Sassari, Italy.

Correspondence to Giuseppe Remuzzi, Mario Negri Institute for Pharmacological Research, Via Gavazzeni 11, 24125 Bergamo, Italy. E-mail gremuzzi@marionegri.it

Insulin resistance, a key component of the metabolic syndrome, is a risk factor for diabetes mellitus and cardiovascular disease. Acetyl-L-carnitine infusion acutely ameliorated insulin sensitivity in type 2 diabetics with insulin resistance. In this sequential off-on-off pilot study, we prospectively evaluated the effects of 24-week oral acetyl-L-carnitine (1 g twice daily) therapy on the glucose disposal rate (GDR), assessed by hyperinsulinemic euglycemic clamps, and components of the metabolic syndrome in nondiabetic subjects at increased cardiovascular risk a priori segregated into 2 groups with GDR 7.9 (n=16) or >7.9 (n=16) mg/kg per minute, respectively. Baseline GDR and systolic blood pressure were negatively correlated (n=32; P=0.001; r=–0.545), and patients with GDR 7.9 mg/kg per minute had higher systolic/diastolic blood pressure than those with higher GDR. Acetyl-L-carnitine increased GDR from 4.89±1.47 to 6.72±3.12 mg/kg per minute (P=0.003, Bonferroni-adjusted) and improved glucose tolerance in patients with GDR 7.9 mg/kg per minute, whereas it had no effects in those with higher GDRs. Changes in GDR were significantly different between groups (P=0.017, ANCOVA). Systolic blood pressure decreased from 144.0±13.6 to 135.1±8.4 mm Hg and from 130.8±12.4 to 123.8±10.8 mm Hg in the lower and higher GDR groups, respectively (P<0.05 for both; P<0.001 overall) and progressively recovered toward baseline over 8 weeks posttreatment. Total and high molecular weight adiponectin levels followed specular trends. Diastolic blood pressure significantly decreased only in those with higher GDRs. Treatment was well tolerated in all of the patients. Acetyl-L-carnitine safely ameliorated arterial hypertension, insulin resistance, impaired glucose tolerance, and hypoadiponectinemia in subjects at increased cardiovascular risk. Whether these effects may translate into long-term cardioprotection is worth investigating.

See the NYBC entry on acetylcarnitine for further information:
http://nybcsecure.org/product_info.php?products_id=118

and acetylcarnitine/Biosint (Italian source):
http://nybcsecure.org/product_info.php?cPath=50&products_id=320

Micronutrients for people with HIV: a low-cost equivalent to K-Pax

K-PAX®, the popular multi-supplement pack, was developed following Dr. Jon Kaiser’s micronutrient study that found an increase in CD4 count among HIV+ individuals using a mix of a potent multivitamin and antioxidants.* At this point, the Medicaid or ADAP formularies of many states include K-PAX®–a validation by the healthcare system welcomed by those of us who have long maintained that supplements can help to address chronic illness. Unfortunately, many people do not have access to these programs and for them, cost can be an issue. (The retail price of the “Double-Strength” K-PAX® formula is about $130/month, quite a sum for those on a budget who face extra healthcare costs.)

That’s why NYBC designed MAC Pack (for Multivitamin Antioxidant Combination), an alternative to the “Double-Strength” K-PAX® formula, based on products already available through our nonprofit co-op. Unlike K-PAX®, the parts of the MAC Pack are delivered in their original bottles, so “some assembly is required” (one reason we also stock small ziplock baggies–great for travel, too!) While NYBC’s MAC Pack is not a precise, 100% match of the K-PAX® formula, it provides a similarly comprehensive vitamin, mineral and antioxidant regimen—and at a much lower cost (about $62/month).

A few small differences between NYBC’s MAC Pack and K-PAX® should be noted:

1) Acetyl L-Carnitine: The MAC Pack actually contains more acetylcarnitine than the double-strength K-PAX®—not a bad idea, especially if you believe, as we do, that acetylcarnitine may be one of the key elements in the multivitamin-antioxidant combination. (Two a day is sufficient if you want to match the K-PAX® formula, but three or more can help if you’re dealing with neuropathy.)

2) Vitamins: The multivitamins contained in the MAC Pack have somewhat different formulas than those in K-PAX®. Taking an extra Vitamin C tab along with the regular multi would make up for one difference. And some might wish to take a bit more calcium and vitamin D3, since bone health remains a concern for people with HIV, and there is also growing recognition of the need for higher doses of D3.

3) Iron: K-PAX® only comes with iron, but for those with liver trouble, this might NOT be a good idea. With the multivitamin Added Protection, you can choose whether to take iron or not (it is available both with iron and without). Also: Ultra Preventive Beta, another Douglas Labs multi, offers a variety of food-based nutrients in addition to a standard multivitamin formula, for $3 more per month.

Note: In 2009, NYBC added to its MAC Pack offerings by introducing the Opti-MAC Pack. This version of the MAC-Pack relies on SuperNutrition’s OptiPack (iron free), which has higher amounts of B vitamins than Added Protection or Ultra Preventive Beta, and so represents a further economy in number of bottles and in cost (about $56/month). Even with these savings, it’s still a close equivalent of the K-PAX®!

For more information on NYBC’s MAC Pack or Opti-MAC Pack, or to place an order, please visit www.newyorkbuyersclub.org, or call 1-800-650-4983. (You can also order the components of the MAC-Pack or Opti-MAC Pack individually.)

REFERENCE:
* Micronutrient Supplementation Increases CD4 Count in HIV-infected Individuals on Highly Active Antiretroviral Therapy: A Prospective, Double-Blinded, Placebo-Controlled Trial. Kaiser JK, Campa AM, Ondercin JP, et al. JAIDS 2006;42[5]: 523-528.

Acetylcarnitine and Alzheimer’s Disease

The Journal of Neuroscience Research featured an article in 2006 on acetylcarnitine and Alzheimer’s Disease (AD)
that outlined the possible mechanism of this supplement in counteracting the effect of AD. Essentially, acetylcarnitine antioxidant workings may be able to prevent, or helpt to prevent, the deformations of brain structure associated with the development of Alzheimer’s. The authors of this NIH-funded research conclude that acetylcarnitine “may be useful as a possible therapeutic strategy for patients with AD.”

For more on this supplement, including its applications for neuropathy, see the NYBC entry Acetylcarnitine.

Acetyl-l-carnitine and L-carnitine: Canadian AIDS Treatment Information Exchange Fact Sheet

Acetyl-l-carnitine (often shortened to acetylcarnitine) and L-Carnitine (aka carnitine) are among the most heavily investigated of dietary supplements for their applications to HIV/AIDS. In particular, acetylcarnitine has been studied for more than a decade for HIV-associated neuropathy, especially by Michael Youle in the UK (see other entries under “acetylcarnitine, this Blog). Acetylcarnitine is also a key component in the K-Pax (and NYBC’s low-cost K-pax equivalent, the MAC Pack). Meanwhile, carnitine is also much used by people with HIV, and the prescription form, Carnitor, is made available through some state-funded formularies.

For a very good overview on acetycarnitine and carnitine research and application to HIV/AIDS, see

Acetyl-l-carnitine and L-carnitine: Canadian AIDS Treatment Information Exchange Fact Sheet

A brief excerpt:

Why do PHAs use this supplement?
Carnitine has many potential uses, including the following:

1. helping to heal damaged nerves—peripheral neuropathy (PN)
2. helping to decrease levels of lactic acid in the blood
3. reducing higher-than-normal levels of cholesterol and/or triglycerides
4. helping to maintain muscle growth

1. To manage peripheral neuropathy (nerve damage causing tingling, numbness or burning in the hands, feet and legs)
Levels of carnitine in the blood are sometimes lower in PHAs with peripheral neuropathy, particularly under the following conditions:

• damage from viral infections such as HIV and CMV (cytomegalovirus)
• the use of “d” drugs such as d4T, ddI and ddC
• the use of some anti-cancer drugs and antibiotics
• alcohol abuse
• diabetes

What the medications in the above list have in common is that they can damage the energy-producing parts of nerve cells—the mitochondria. Injured mitochondria cannot supply sufficient energy and nerves begin to malfunction and can die. Nerves in the feet, legs and hands, particularly in the skin covering those body parts, appear to be especially susceptible to PN. Some researchers have noticed that PHAs with PN can develop abnormal sweating, suggesting that nerves in sweat glands can also be affected.

One formulation of carnitine, acetyl-L-carnitine (ALCAR), may play a role in the management of PN. This compound helps mitochondria function and also appears to enhance the effect of a chemical that helps nerves grow—nerve growth factor.

Researchers in England conducted an extensive study of ALCAR in PHAs with peripheral neuropathy. Their findings revealed that most PHAs showed some degree of recovery from nerve damage after taking ALCAR 1.5 grams twice daily for up to 2¾ years.

See also the NYBC entry on acetylcarnitine. Like its predecessor DAAIR, NYBC has this key supplement manufactured by pharmaceutical-grade producer Montiff; this allows for considerable cost savings for co-op buyers compared to commercially available products.

Acetyl-l-carnitine and alpha lipoic acid in combination show an anti-aging effect in animal models

The Oregon State University/Linus Pauling Institute website is highlighting a number of recent studies, especially from 2005-2006, which have examined the potential of acetyl-l-carnitine or L-carnitine, together with alpha lipoic acid, to counter the effects of aging in laboratory rats. Like the Linus Pauling Institute reviewer, we are looking forward to human clinical trials in the next few years to further define useful dosages and health benefits.

NOTE: a great deal of previous research on acetylcarnitine, L-carnitine, and alpha lipoic acid is reviewed on the NYBC website.

…two studies found that supplementing aged rats with either ALCAR [acetyl-l-carnitine] or alpha-lipoic acid, a mitochondrial cofactor and antioxidant, improved mitochondrial energy metabolism, decreased oxidative stress, and improved memory. Interestingly, co-supplementation of ALCAR and alpha-lipoic acid resulted in even greater improvements than either compound administered alone. Likewise, several studies have reported that supplementing rats with both L-carnitine and alpha-lipoic acid blunts the age-related increases in reactive oxygen species (ROS), lipid peroxidation, protein carbonylation, and DNA strand breaks in a variety of tissues (heart, skeletal muscle, brain). Improvements in mitochondrial enzyme and respiratory chain activities were also observed. While these findings are very exciting, it is important to realize that these studies used relatively high doses (100 to 300 mg/kg body weight/day) of the compounds and only for a short time (one month). It is not yet known whether taking relatively high doses of these two naturally occurring substances will benefit rats in the long-term or will have similar effects in humans. Clinical trials in humans are planned, but it will be several years before the results are available.