One of the most vexing issues I’ve had to deal with since I started exploring alternatives to ART (antiretroviral therapy) for keeping my immune system as healthy as I can, is my inability to abide by some of the most basic rules of scientific research. I’m not beating myself up too much for this failure, as any “experiment of one” is bound to encounter these limitations.
I have not had the luxury of time or discipline to adopt a single particular therapy, and then measure the results and compare them to other therapies. More typically, I am trying multiple, sometimes complimentary, and sometimes even contradictory strategies at once, making it impossible to determine any definitive effect of the individual components. Such was the case with my experience with MAF 314, a natural fermented food product developed by Italian researcher Marco Ruggiero, which I was able to access, under the direction of one of my physicians. I started making and consuming MAF 314 the first week of April last year, about six weeks before I started taking antiretroviral drugs (ARVs) again on May 23.
Anyone who follows my story knows how hard I try to track and analyze my progress, including surrogate laboratory markers. Indeed, I spent many words, considerable time, and even produced a video a couple of weeks ago, showing how ARVs dramatically dropped the PCR RNA (viral load) markers and halted the decline in CD4 counts. I’m still fairly confident that both of those changes were primarily due to ARVs.
However, the third set of markers I shared—a chart showing significant improvement in Organic Acid Test (OAT) markers, after starting ARVs again—needs some clarification, if not revision. OAT is a complex set of more than 70 different markers, grouped broadly in the following categories:
- Intestinal Microbial Overgrowth (8)
- Malabsorption and Bacterial Markers (9)
- Oxalate Metabolites (3)
- Glycolytic Cycle Metabolites (3)
- Krebs Cycle Metabolites (6)
- Neurotransmitter Metabolites (7)
- Pyrimidine Metabolites (2)
- Ketone and Fatty Acid Oxidation (8)
- Nutritional Markers (9)
- Indicators of Detoxification (3)
- Amino Acid Metabolites (14)
- Bone Metabolites (1)
I’ve written about organic acid tests before, and I still find them to be some of, if not the most useful indicators of my progress in addressing the underlying causes of my health issues. However, it’s not so simple as comparing the total number of markers that are out of range from one test to the next, as I did on the chart I used , for a number of reasons.
First of all, the entire category of “nutritional markers” is misleading. Of the 15 times I’ve been out of range on one of those markers, for example, only once was it due to a deficiency (vitamin C, of all things). The other 14 markers were always high. No doubt that is because, until I restarted ART, I was supplementing a lot, causing those nutritional markers to be high. Including high levels of B vitamins, NAC and ascorbic acid as “out of range” contributed to distorting the significance of more important markers of deficiency and dysfunction.
In my defense, I did disclaim in the video that I was trying to condense a lot of data to make a point, but after reviewing these markers more closely, I’m much less likely to give ARVs alone credit for changing them in a positive way, and I am now inclined to think that the MAF 314 was a more significant factor. If you’re interested in knowing why, bear with me, as it gets a bit complex.
Instead of a chart, I need to use a spreadsheet to explain what has been happening to those markers. For each OAT category above, I will be presenting a series of numbers that represent how many markers in each category were out-of-range, sequentially over five tests, from December 2010, through August 2012. Like this: 1-2-3-4-5. Pay special attention to the last two numbers, as those represent the change in marker counts before and after I started taking ARVs, as well as MAF 314. Most of the information I am sharing concerning the significance of individual markers is from the detailed analyses that accompany the OAT results.
Intestinal Microbial Overgrowth and Malabsorption and Bacterial Markers
For example, the 17 markers in these first two categories primarily represent evidence of yeast, fungal and bacterial overgrowth. The number of markers out of range for these categories, sequentially over the series of five tests were: 7-7-5-3-3. The number of markers that are out of range has been steadily declining, as they should be, considering some of the extreme measures I’ve taken since the first OAT test, including high dose intravenous vitamin C, ultraviolet blood irradiation, extensive regimens of alternative nutritional-based anti-fungals, probiotics and prebiotics, and finally, the ARV monotherapy I’ve been on.
However, there was no change in these markers as a result of either 3 months on the protease inhibitors or 4 months of MAF 314.
I have high levels of oxalic acid in all five tests. This concerns me, as I have a history of kidney stones, but what does get my attention is this: “Besides being present in varying concentrations in most vegetables and fruits, oxalates, the mineral conjugate base forms of oxalic acid, are also byproducts of molds such as Aspergillus and Penicillium and probably Candida. If yeast or fungal markers are elevated (they are), antifungal therapy may reduce excess oxalates…” It is also possible that the elevated marker is the result of high dose IVC, or even a genetic hyperoxaluria.
This marker has been out of range, regardless of what I am doing. Hopefully I can rule some things out if improvements in the yeast and fungal markers continue.
Glycolytic Cycle Metabolites
There has only been one marker very slightly out of range in the Glycolytic Cycle Metabolites section, so let’s move on.
Krebs Cycle Metabolites
There has been one marker in the Krebs Cycle section that has been out of range more often than not, and that is succinic acid, which is also included in the Malabsorption and Bacterial Markers section above. It may also be an indicator of nutritional deficiency, specifically riboflavin and/or coenzyme Q10, and the slightly elevated blip for malic acid on the first test would seem to support that.
There was no change in this marker during ARV or MAF 314 therapy.
I am presenting this information in the same order as the test results are reported, but this category should probably be moved to the top of the list. I hope that by now everyone reading this understands the numbering system I am using here. In this section, I had 4 out of 8 markers out of range on my first OAT test in 2010, with every subsequent test showing 3 or 4 out of 8 total markers out of range. One of them, quinolinic acid, was nearly 4 times the upper range limit prior to the last test.
High quinolinic acid may be a sign of inflammation and/or neural excitotoxicity. Quinolinic acid is derived from the amino acid tryptophan and is neruotoxic at high levels. As an excitotoxic stimulant of certain brain cells that have NMDA-type receptors, high quinolinic acid may cause nerve cell death with continuous stimulation. Brain toxicity due to quinolinic acid has been implicated in Alzheimer’s disease, autism, Huntington’s disease, stroke, dementia of old age, depression, HIV-associated dementia, and schizophrenia…
Treatment of excessive levels of quinolinic acid can be achieved by multiple approaches: reducing tryptophan supplements, preventing repeated infections and subsequent immune modulators like inerferon that increase quinolinic acid production; or reducing the numbers of vaccines given at one time or increasing the interval between vaccinations. In addition, the drug deprenyl or the dietary supplements carnitine, melatonin, capsaicin, tumeric (curcumin) and garlic may reduce brain damage caused by quinolinic acid. Niacin (nicotinic acid) and miacinamide may also reduce quinolinic acid production by decreasing tryptophan shunting to the quinolinic acid pathway. Inositol hexaniacinate as an adult dose of 500-1000 mg does not cause niacin flush. A high quinolinic acid/5-hydroxyindoleacetic acid ration would be indicative of immune overstimulation and/or phthalate toxicity.
The Quinolinic/5-HIAA Ratio has also been very high—6 to 8 times the upper limit until the last test result.
An elevated ratio is not specific for a particular medical condition and is commonly associated with excessive inflammation due to recurrent infections…. Immune overstimulation, excess adrenal production of cortisol due to stress, or high exposure to phthalates may also increase the quinolinic acid/5-HIAA acid ratio.
This category of neurotransmitter metabolic markers accounts for the a substantial portion of the decrease in overall markers out-of-range that I was trying to demonstrate with a chart a few weeks ago. It is also a subset of markers that seem likely to be affected at least as much by the use of MAF 314 as by protease inhibitors, though I cannot rule out some sort of symbiotic effect either. I hope to nail this down a bit better by continuing to monitor this marker on future tests.
Considering that the most persistent and disabling symptoms that I have had to deal with the last decade or more are neurological ones, such as fatigue, depression and “brain fog”, that can be associated with high levels of quinolinic acid (QA), this marker has risen to the top of my list for monitoring. The role of QA is being researched in several disorders, including Alzheimers and “AIDS dementia complex” (ADC), as well as depression and fatigue.
Most interestingly, QA has been identified as a key player in irritable bowel syndrome, which seems to affect a lot of gay men. No one seems to want to connect the dots between IBS and what used to be called “Gay Bowel Syndrome” in the pre-AIDS 1970s, but there you have it. IBS/GBS is more than just diarrhea and leaky gut, though those two conditions obviously exist. There has been considerable new research in the intricate connection between the gut and the brain.1,2
No markers out of range, so no need to dwell on them here.
Ketone and Fatty Acid Oxidation
Here’s what the OAT reports says about these markers.
High [fatty acid markers] may be due to fatty acid oxidation disorders, carnitine deficiency, fasting, or to increased intake of the medium-chain triglycerides found in coconut oil, MCT oil and some infant formulas. The fatty acid oxidation defects are associated with hypoglycemia, apnea episodes, lethargy, and coma. [An acetyl carnitine profile… can rule out fatty acid oxidation defects.] Regardless of cause, supplementation with L-carnitine or acetyl-L-carnitine (500-1000 mg per day) may be beneficial.
This is the only significant category besides Neurotransmitters that showed a change after I resumed ARVs and started consuming MAF 314. There are no markers currently out of range in this category, according to the last test available to me.
It will be interesting to see if this category remains in range on the next round of OAT, which I just recently submitted, as I have not been using MAF 314 for several months. There is a connection between fatty acid oxidation and the mitochondria, another topic I will be addressing in the near future.
Again, I am only including this section in the interest of complete disclosure, as I do not consider them to be significant markers of change in my overall health status. These markers mostly reflect excreted vitamin levels, though one critically important antioxidiant, N-acetylcysteine is included. I am more concerned when these markers are not elevated, such as the one time my vitamin C level was quite low, or the latest test, showing no NAC at all. Not good. The fact that the last test had only one out of range marker is a reflection of the fact that I had pretty much quit most nutritional supplementation while taking the protease inhibitors, mainly because doctors at the Mayo Clinic insisted there was a high risk of interactions, I chose to eliminate them, rather than risk having them used as an excuse for drug failure.
Indicators of Detoxification
The two out-of-range markers on the third test were only slightly elevated. The analyses suggested a correlation with gut dysbiosis (no surprise there) and possible glutathione deficiency, which I am monitoring. No change in the last two tests, so let’s wrap this up.
There has been a huge increase in interest and research about the role gut health plays in our overall health, from immune status to mood and energy. Indeed, the gut has even been nicknamed “the second brain,” because it is filled with neural tissue and neurotransmitters and because it is in constant communication with the brain. I can find no references that suggest that ARVs are beneficial to the gut microbiome, or improve neurotransmitters there, but there are lots of papers making that case for probiotics. MAF 314 is more than “just” a probiotic. It is a super-probiotic, containing more than 20 strains of beneficial microbes.
So, in terms of OAT markers, my gut inclination is to give my nod and acknowledgement for improvement to MAF 314, rather than ARVs.
Poop: the ultimate marker
One other thing I’ve learned the last decade or so is that the efficacy—or lack of efficacy—of a therapy may become obvious only after stopping treatment. This is how I finally became convinced that warfarin, for example, was the only option that has so far been proven to prevent recurring DVT blood clots, for example. Every time I stop taking the drug, I get another DVT. It is also how I discovered that I could maintain acceptable surrogate marker levels for a decade, without the use of ART.
At the risk of sharing too much information, one of the things that has been a more-or-less persistent problem since becoming sexually active in my 20s, is intestinal distress, specifically, loose stools and diarrhea. That problem peaked while I was taking ARVs in the late 1990s and 2000s, but amazingly cleared completely during the time I was taking MAF 314. I would actually brag to clinicians about how proud I was of perfect stools. Not too hard, not too soft, perfect in every way.
Since running out of MAF 314 late last year, the diarrhea has returned, and times with a vengeance. It is embarrassing to recall an incident, fortunately at home, when I accidentally soiled myself, thinking I merely needed to pass some gas. Diarrhea is one of the most frequently reported adverse effects of protease inhibitors, including darunavir, and that is the culprit, I suspect, despite the fact that I am taking the drug at reduced dose.
The problem of loose stools and diarrhea is resolving, now that I’m on my second week of restarting MAF 314. I’m not ruling out the possibility that other probiotic interventions might have accomplished the same thing, but it is not for lack of trying on my part. I’ve tried incorporating probiotic supplementation for years, but never achieved the level of success, in terms of consistent, normal stools, that I’ve had with MAF-314.
More information about MAF 314