MSM in HAND

HIV-Associated Neurolocognitive Disorders (HAND), as well as peripheral neuropathy, affects a significant number of people with HIV. It may manifest mildly or progress to more serious conditions. These include peripheral nerve pain (neuropathy), coordination problems, cognitive and memory trouble to dementia—and this sometimes in spite of antiretroviral therapy.

Research is uncovering how this disease manifests—and some ideas about how to intervene. These data underscore aspects of HIV disease that contribute significantly to the progression of the disease, resulting in damage to the neurological system manifesting as cognitive defects and/or peripheral neuropathies. Part of what happens with HIV is that the body’s response is excessive, causing increased oxidative stress.

HIV proteins like tat can damage cells by inhibiting a regulator gene of redox reactions and detoxification known as nrf2. Normally, when this gene is induced (activated) in response to increased amounts of free radicals, it in turn activates other genes like SOD and catalase, the body’s system of transforming potentially damaging free radicals into water or other innocuous substances. This helps protect healthy cells–and often neurons, not infected by HIV directly, are damaged by the release of excessive amounts of free radicals.

Maintaining an appropriate redox balance is key, as these free radicals are also part of the bodies immune defenses that help to kill infected cells. One problem in HIV is that many cells that die, most CD4 T-lymphocytes and neurons, for example, aren’t infected. But they die due in part to oxidative stress

So what to do? There are data on ways to manage neuropathy, including using 3 grams per day of acetylcarnitine or the judicious use of Cannabis sativa. A drug derived from Tripterygium wilfordii called Celastrol has shown some early promise. In addition, the Men Who Have Sex with Men supplement can help! Woops, wrong acronym. MSM here represents methylsulfonylmethane, often used in formulae to help join function or on its own. Unfortunately, these are only animal studies so we don’t have information on how or if it will help in offsetting HIV-related cognitive disorder.

Could we ever get a clinical trial?

*******************************************

Abstracts:

Am J Transl Res. 2015 Feb 15;7(2):328-38. eCollection 2015.

MSM ameliorates HIV-1 Tat induced neuronal oxidative stress via rebalance of the glutathione cycle.

Abstract

HIV-1 Tat protein is a key neuropathological element in HIV associated neurogcognitive disorders (HAND); a type of cognitive syndrome thought to be at least partially mediated by increased levels of brain reactive oxygen species (ROS) and nitric oxide (NO). Methylsulfonylmethane (MSM) is a sulfur-containing compound known to reduce oxidative stress. This study was conducted to determine whether administration of MSM attenuates HIV-1 Tat induced oxidative stress in mouse neuronal cells. MSM treatment significantly decreased neuronal cell NO and ROS secretion. Further, MSM significantly reversed HIV-1 Tat mediated reductions in reduced glutathione (GSH) as well as HIV-1 Tat mediated increases in oxidized glutathione (GSSG). In addition, Tat reduced nuclear translocation of nuclear factor-erythroid 2 p45-related factor 2 (Nrf2), a key nuclear promoter of antioxidant activity, while MSM increased its translocation to the nucleus in the presence of Tat. These results suggest that HIV-1 Tat reduces the resiliency of neuron cells to oxidative stress which can be reversed by MSM. Given the clinical safety of MSM, future preclinical in vivo studies will be required to further confirm these results in effort to validate MSM as a neuroprotectant in patients at risk of, or who are already diagnosed with, HAND.

***

Toxicol Appl Pharmacol. 2014 Oct 1;280(1):42-52. doi: 10.1016/j.taap.2014.07.010. Epub 2014 Jul 23.

Celastrol ameliorates HIV-1 Tat-induced inflammatory responses via NF-kappaB and AP-1 inhibition and heme oxygenase-1 induction in astrocytes.

Abstract

HIV-1 Tat causes extensive neuroinflammation that may progress to AIDS-related encephalitis and dementia. Celastrol possesses various biological activities such as anti-oxidant, anti-tumor, and anti-inflammatory activities. In this study, we investigated the modulatory effects of celastrol on HIV-1 Tat-induced inflammatory responses and the molecular mechanisms underlying its action in astrocytes. Pre-treatment of CRT-MG human astroglioma cells with celastrol significantly inhibited HIV-1 Tat-induced expression of ICAM-1/VCAM-1 and subsequent monocyte adhesiveness in CRT-MG cells. In addition, celastrol suppressed HIV-1 Tat-induced expression of pro-inflammatory chemokines, such as CXCL10, IL-8, and MCP-1. Celastrol decreased HIV-1 Tat-induced activation of JNK MAPK, AP-1, and NF-κB. Furthermore, celastrol induced mRNA and protein expression of HO-1 as well as Nrf2 activation. Blockage of HO-1 expression using siRNA reversed the inhibitory effect of celastrol on HIV-1 Tat-induced inflammatory responses. These results suggest that celastrol has regulatory effects on HIV-1 Tat-induced inflammatory responses by blocking the JNK MAPK-AP-1/NF-κB signaling pathways and inducing HO-1 expression in astrocytes.

Micronutrient Article Error

One of the figures in our micronutrient article is wrong–and in fact, it is perhaps the most important one of the paper. The correct figure is attached below and is the one that we originally submitted. The error doesn’t change our findings–these figures have the effect of showing what we found in a graphic. The wrong one tells the story that we found nothing important! The correct one shows how robust our findings actually are.

We are in the process of correcting the error with PLoSOne and will be preparing a more formal response. In the process of re-sizing the figure for editing purposes this past February, an earlier figure was used. This version appears to show no effect from the intervention.

Some might presume that this means we merely cherry-picked the data to find a palatable solution. That would be incorrect as the initial analysis was faulty. Further, the frequentist analysis underscores by comparison our findings of a robust effect.

Our team had, in setting up the analysis, initially used a VERY flat prior probability. This had the effect of squashing the data and distorting such that it no longer reflected the original findings of the studies we were analysing. The reason we can be sure this is the case is that the result did not resemble the original data. I.e., the original data was in fact, for example, Fawzi 0.56 (0.32, 0.98). You can see that clearly in the frequentist analysis (supplementary figure 1).

Upon adjusting to a more accurate scale factor, the result was a strong effect for the impact of a simple multi on the rate of HIV disease progression.

S1 Fig. Forest plot of rate of HIV disease progression, frequentist analysis.

A frequentist analysis yielded a similar 40% reduction in the rate of progression to clinical disease stages (RR 0.60, 95% CI 0.46, 0.78; p = 0.00008) for subjects on MNS, when including supplement arms that included a MNS alone or MNS plus either zinc or selenium.

doi:10.1371/journal.pone.0120113.s001

This underscores also the importance of scrutinizing closely the way data are handled and analyzed. As I have learned over the years in doing this work, a preferred answer may indeed be produced. But in this case, the answer reflects the actual data of the original studies.

George M. Carter

Fig. 2 Bayesian Analysis

Multi Slows Disease Progression

A meta-analysis has been published that reviewed the clinical studies that looked at the use of a multivitamin in people with HIV. There was enough data of people not yet on antiretrovirals and we showed a significant effect on how fast AIDS develops after HIV infection (the progression rate).

CONCLUSIONS: MNS significantly and substantially slows disease progression in HIV+ adults not on ARV, and possibly reduces mortality. Micronutrient supplements are effective in reducing progression with a posterior probability of 97.9%. Considering MNS low cost and lack of adverse effects, MNS should be standard of care for HIV+ adults not yet on ARV.

There was also evidence that it could reduce the risk of dying (mortality). There weren’t enough studies to assess the effect of a multi among those on ARV, though these studies are also discussed.

The first author of the study was NYBC’s George Carter, who was working as part of an NIH grant with colleagues at Mount Sinai in New York.

 

NYBC’s HIV+Aging Series Continues, Now Online!

haught-dec2-event-speaking
Jackie Haught offered personal insights into healing from her 30 years as an acupuncture practitioner.

In recognition of World AIDS Day 2014, New York Buyers’ Club hosted another installment in our ongoing free public seminar series, HIV+AGING. Held Tuesday December 2nd at City University of New York’s Graduate Center in Manhattan, the workshop was a great success and – like any good show – left folks craving more.

This thirst can now be slaked online – on NYBC’s new YouTube page, now featuring excerpts from the December 2 event – with more to come in the future!

YouTube-NYBC-slug

 

HIV+AGING: What Can Complementary & Alternative Medicine Do for You? featured three outstanding and personable speakers presenting valuable information and insights gleaned from their years of experience in the field of health and HIV.

Panelists included: Dr. Vani Gandhi, Director of Integrative Medicine at Spencer Cox Center for Health at Mount Sinai’s St. Luke’s and Roosevelt Hospitals; Jackie Haught, Founder of Blue Lotus Acupuncture Center in NYC and an acupuncture practitioner for more than 30 years; and NYBC’s own Treatment Director, George Carter, also President of Foundation for Integrative AIDS Research.

Presentations were followed by a hearty and heartfelt Q&A session: attendees not only posed pertinent questions to the panelists, but also opened up with one another about their own personal “CAM” experiences, both positive and frustrating.

We are already planning the next event and welcome collaborators!

Tune in to New York Buyers Club’s new YouTube channel for excerpts from our latest HIV+AGING event and more.

New @ NYBC – February 2015

supplement-header-2014These New Products and More
Available Through NYBC’s Newly-Redesigned Website & Co-Op Store

mega-pc-35-lecithin-1200mgMega PC-35 Lecithin – (Jarrow Formulas, 120 x 1200 mg; $9.75) Each softgel contains 1200 mg lecithin with choline 57 mg (from 35% PC lecithin) and 420 mg of phosphatidylcholine derived from soy. Phosphatidylcholine is a compound containing different types of fatty acids, glycerin, phosphorus and choline (a nitrogen-containing base). This may be an excellent product for people with hepatitis B or C, according to one well-designed study using 3 grams per day. Other benefits may be for mood enhancement for those with neurological disorders, to enhance cardiovascular health (in the context of a better diet), and possibly preventing or treating gallstones.

betaine-plus-pepsin-100-capsFor digestive health, NYBC is now carrying Twinlab’Betaine HCL Caps (100 caps $9.50). Each capsule contains betaine (as betaine hydrochloride) – 648 mg plus pepsin, 130 mg.

The addition of pepsin is thought to significantly improve the ability of the betaine to help the stomach lower the pH, that is, make the stomach more acid. That first amount of hydrochloric acid that your food hits arriving in the stomach is a crucial part of digestion. Betaine is typically used for people with a condition of low stomach acidity known as hypochlorhydria. This may actually be the problem even though one has reflux. It is a fairly common finding, for example, among people living with HIV, among a range of other conditions. Supplementing with betaine can help to improve digestion IF this is the case. Getting properly diagnosed before trying this is critically important. A 2013 study among healthy adults who had chemically-induced reduction in gastric acid (e.g., through proton-pump inhibitors) saw a reduction in stomach pH when given betaine supplements.

Uridine-5-monophosphate, 60 capsules for $22.20 from Jarrow. Each capsule contains 250 mg Uridine-5’-monophosphate disodium salt. Uridine is one of the nucleotides that is used by the RNA molecule. It is found in abundance incorporated in the phospholipid membranes of neural (especially brain) tissue. Data are limited but suggestive of benefits for memory and liver function. This is not dissimilar to an intervention utilized to help minimize mitochondrial toxicity associated with some antiretroviral drugs. One study suggested this could reduce damage to AZT or d4t (stavudine or Zerit)-related mitochondria, however, markers of inflammation were worsened. So this one should probably be used in the context of an anti-inflammatory protocol such as including carnitine, NAC, alpha lipoic, curcumin, omega-3 fatty acids and the like, which are a good idea anyway to keep TNF, IL-6 and hsCRP in check.

Astaxanthinastaxanthin-12-mg-30 12 mg – 30 softgels $16.25 from Jarrow Formulas. Astaxanthin is one of the many varieties of carotenoids (beta-carotene being one of the longest known and best characterized). Studies are somewhat mixed on the benefits of this agent to offset oxidative stress induced by exercise, with some benefit seen among soccer players and none for cyclists. One study using a mix of carotenoids showed an enhancement of visual acuity. Other small studies suggest benefits for increasing HDL, skin tone, and reflux frequency.


Garlic & Allicin  Sadly, NYBC no longer carries Dr. Zhang’s popular Allicin supplement,garlicell and arlipure however we have found these two excellent substitutes that indicate the amount of allicin and other components on the label. GarliPure from Natrol (120 “odor controlled” caps for $17). Each capsule contains 750 mcg of allicin along with 7.5 mg gamma glutamyl-cysteine, 5 mg allicin, 4 mg sulfur and 800 mcg of thiosulfinates, and GarliCell.
Source Naturals’ GarliCell features “no after-odor.” Each $14 bottle has 90 tablets; each tablet contains 6 mg (6000 mcg) of allicin along with 4.2 mg sulfur and 6 mg of thiosulfinates. Allicin is thought to possess the greatest activity of garlic’s various components. Early studies showed some pretty robust effects on cryptosporidiosis. Aside from anti-infective activity, there may be some benefit for maintaining a healthy blood lipid profile.


New Strengths + Sizes…

NYBC is now carrying a few new strengths and sizes of customer favorites. Our ever-popular “house brand” of CoQ10, Jarrow’s CoQ10 Q-Absorb, now is available in a very economical 120 x 100 mg softgel size for only $29. For those seeking a higher dose, we now also have CoQ10 400 mg (60 softgels) from Protocol for Life at $44.50.

curcumin-phytosome-jarrow-500-mg-60cNYBC has also picked up Jarrow Formulas‘ new Curcumin Phytosome (each cap 500 mg curcumin phytosome-phosphatidylcholine complex with 18-22% curcuminoids), a formulation that may further improve the absorption of curcumin. In the Ayurvedic tradition, recipes often include honey or black pepper, today known to enhance the body’s ability to absorb this increasingly important and well-researched anti-inflammatory agent.

Also new at NYBC…

calcium-blend-iron-free-easy-swallow-180A very moderately priced B100 (B Complex) from Twinlab for $11.75 that contains  100 mg of eachof the B-vitamins (and 100 mcg of B12). Each bottle, 100 capsules… Borage (Jarrow Formulas; 120 sg for $16.25) Provides one gram of polyunsaturated fatty acids from the Borago officinalis plant, including 240 mg of gamma linolenic acid (GLA/omega-3) and other fatty acids. This is a good source of GLA, especially in combination with flaxseed oil … New variation on SuperNutrition‘s Calcium Blend, an iron-free, easy-swallow formulation, same price ($14.25) and strength – just smaller (and more!) tablets.

In The News: CoQ10 Proves Its Worth Again

Heart To Heart: News & Tips For A Healthy Heart

New research on the supplement CoQ10, recently published in American and European medical journals, shows that it increases survival rates and decreases hospitalizations for people being treated for heart failure. CoQ10 (also called Coenzyme Q10, among other names) is a powerful antioxidant and acts as an essential factor in the heart’s energy production. In the past, clinical studies have provided evidence of its value as an adjunct treatment for angina, congestive heart failure, arrhythmia, and hypertension (high blood pressure). In addition, researchers have found that statin drugs deplete CoQ10, and so it has been suggested that people taking these cholesterol-lowering drugs should also use CoQ10 to support healthy heart function.

CoQ10 (also called Coenzyme Q10 and ubiquinone, among other names) is a powerful antioxidant and acts as an essential factor in the heart’s energy production. A naturally occurring and powerful antioxidant nutrient, it retards free radical formation in biological systems, and resembles vitamin E and vitamin K in chemical structure. Biochemically, it functions much like vitamin E in that it participates in antioxidant and free radical reactions. 

NOW AVAILABLE FROM NYBC’S ONLINE CO-OP:
Jarrow Formulas’ Q-Absorb, available in two strengths, utilizes a “completely natural proliposome lipid soluble delivery system clinically shown in humans to increase Co-Q10 levels up to 400% – three to four times better absorbed than chewable Co-Q10 tablets.” Price: $21- $29.

Douglas Labs’ Cardio Edge* employs plant sterols (phytosterols) from soy, Sytrinol (a proprietary extract of polymethoxylated flavones and tocotrienols from citrus and palm fruits), and pomegranate extract. Their Ultra Coenzyme Q10 ($121.60) has 60 chewable tablets with 200 mg CoQ10 combined with 500 mg lecithin.

* Note: Prices on Douglas Labs’ products are considerably lower for NYBC members!

The study lasted for two years and compared heart failure patients taking 100mg CoQ10 three times per day with patients who were not taking the supplement. By the end of the two-year period, the CoQ10 group showed a significantly lower rate of hospitalization for heart failure, significantly better functional capacity, and a significantly lower rate of death from cardiovascular disease.

NYBC has stocked CoQ10 since our founding, and has recently expanded its offerings. We’re happy that we’ve been able to provide this important supplement at discounted prices to our members over the years, and we’re happier still to see this new research strengthening the case for a supplement that already had a considerable amount of evidence demonstrating its benefit for heart health.

Here are some additional NYBC suggestions for cardiovascular health. All are based on our reading of the always-evolving research on nutrition and nutritional supplements:

Eating fatty fish (such as wild salmon) once or twice a week is an excellent approach to maintaining cardiovascular health; however, regular supplementation with fish oil can also provide the omega-3 fatty acids (called DHA and EPA) that have been closely linked to cardiovascular benefit. Note that supplements, when properly purified, avoid the problem of mercury contamination, a concern for those who eat sea food regularly.

Niacin, a B vitamin, is still one of the best agents for supporting cardiovascular health. In a long-term study, it was associated with lower risk of cardiovascular disease and death related to cardiovascular disease. (Don’t be misled by some recent reports about Niacin’s lack of effect, which only appeared in a study using a particular form of the supplement together with a statin drug.) The main drawback of Niacin is that it may cause flushing and itching, which make it difficult or impossible for some to take. Starting with a low dose of about 100 mg and working up to about 1,000 mg per day may minimize this reaction.

Other helpful agents include carnitine (which may lower triglycerides), pantethine (a B vitamin) and phytosterols, such as those in Douglas Labs’ CardioEdge.

Acetylcarnitine Gets Credit

Don’t let the icky generic packaging fool you! All NYBC products and vendors are carefully vetted and hand-picked. The manufacturer here, Montiff, produces our “house brand,” N-Acetyl-L-Carnitine (90 capsules; 500 mg ea acetyl-L-carnitine), as well as our proprietary ThiolNAC (which we unfortunately just ran out of stock of).

 

Longtime NYBC Favorite for Neuropathy Gets Its Due

A 2013 review by neurology experts found confirmation of the benefits of acetylcarnitine (also called N-acetyl-L-carnitine) supplementation for diabetes-related neuropathy (=nerve pain and damage), for HIV and antiretroviral therapy-related neuropathies, for neuropathy caused as a side effect of chemotherapy, and for neuropathy caused by compression (like sciatica). According to the review, acetylcarnitine “represents a consistent therapeutic option for peripheral neuropathies.”

Furthermore, recent research on acetylcarnitine has provided new insights into how the supplement works to diminish the pain of neuropathy and promote the regrowth of damaged nerve tissue.  That’s why the authors of the review conclude that the recently expanded knowledge about acetylcarnitine’s mechanism of action can open up “new pathways in the study of peripheral nerve disease management.”

We’re glad to see confirmation of earlier findings about the value of this supplement for conditions like the peripheral neuropathy experienced by people with HIV—NYBC has been recommending it for that purpose for many years.

We hope that this review will lead to even wider recognition in the medical community of the value of acetylcarnitine as a therapy for neuropathy.  It’s time this supplement got its due!

 

Want to know more about amazing acetylcarnitine?
This blog has 26 related articles about acetylcarnitine!