Wednesday, March 25, 2009

How am I doing?

A friend asked last week: "Forget all the technical stuff. How are you doing?"

No easy answer.
"Fine" for acquaintances.
"Discouraged for the doctor.
"Cosi cosi" for everyone else -- an Italian expression meaning a little of this, a little of that, another way of saying "I don't have the slightest idea!"

In this illness (or if you prefer, alphabet clusters of closely-related syndromes -- CFS, ME, Lyme, PTSD, MCS, FMS) there are so many variables that it is hard to know. For every thing starts working better, another thing seems to get worse. Like life, there is a mix. We can choose where to direct our attention. If we are optimists, as I tend to be, we may sense improvement even if it's illusory. Vice versa if we tend to be pessimists. So here's a long answer to a short question.

On the good side---
I am feeling more energy. I’ve taken my body temperatures a few times when I’ve felt particularly good and found it at 98.2. I’ve had some awful days, but they’ve been offset with several days in which I feel better than I have in quite a while. I take this as a sign I am making progress.

Another good sign is that I have been able to increase my B-12. Remembering how too much B-12 kept me up at night, I gingerly broke a pill in half and still managed to sleep that night.

A mixed sign: I am sleeping 8 to 10 hours at night. Wow! During years of insomnia, this would have felt like the answer to my prayers. Now I would like to do something more interesting with my time. (I'm not even having wild dreams!) Logging in all these nighttime hours doesn't erase my need for a mid day nap. How do I interpret this one? Am I worse because I'm more fatigued, or better because my nervous system is calming down enough to sleep? I choose the latter interpretation with no evidence other than a preference for optimism.

Now for the bad news...

Even though my sulfate levels are in a good (supposedly therapeutic range) my urinary ammonia levels are not. But high ammonia is not so good for the brain, or the other tissues in the body. And I don't know how to bring them down while eating protein.

The protocol Yasko uses for autistic kids, and Roberts uses for heart disease patients, involves a low protein diet to control the drain of metabolites through the transulfurate pathway (subject of last two posts). But many people with CFS and FMS cannot manage on low protein because our amino acids are already low.

I've had amino acids tested (plasma and urine) since 2000 and they are always low. They actually get lower when I eat more protein! Researchers at the University of Pisa just published a study showing that people with FMS tend to have many low amino acids. Here is the link and abstract. Clinical Biochemisty March 10 2009
OBJECTIVES: To evaluate plasma amino acid (AA) concentrations in patients affected by fibromyalgia (FM) and to study the relationships between their levels and FM clinical parameters. DESIGN AND METHODS: 20 AAs were assessed in 34 FM patients and in 18 healthy volunteers by means of a modified version of the Waters picotag method. RESULTS: Significant lower plasma taurine, alanine, tyrosine (Tyr), valine, methionine, phenylalanine and threonine concentrations, and the sum of essential AAs were observed in FM patients vs healthy controls (P<0.05). Tyr CAA' ratio and the sum of AAs competing with tryptophan for brain uptake were significantly reduced in FM (P<0.05). A significant correlation was found between FM clinical parameters and certain AAs.

Aside: I have a way of checking them at home that I learned from Dr. Charles McWilliam’s in Nevis (Talk about traveling distances for medical care! I went there as a student of his method of using colored light to do past-life regressions, in another lifetime.) Nevis is a Caribbean island adjacent to St. Kitt’s, close to the equator, with a huge volcanic mountain in the center, turquoise seas, white sand, coconut trees, and lots of goats and donkeys wandering around on trails through the hills.

So what am I to do? I eat more protein, ammonia climbs. Hmmmm..... something else is awry. After two repeats, I pulled out the other testing substrate to look at urinary urea. Low. Bummer. This all means I am breaking down proteins but not recycling amino acids adequately through the urea cycle.

No pre-protocol baseline on the ammonia/urea/sulfates to show if I am better or worse, or unchanged, but I do have one external sign: I had to reduce my weights at the gym when I started this protocol and have not been able to raise them to my mid-December levels after nearly three months!

Bad news # 2. I have a home test kit that measures antioxidant need. It does this by indicating the level of malondialdehyde (MDA) in the urine. MDA is the first byproduct of lipid peroxidation (damage to the fatty acids of cell membranes). Free radicals are always being produced in our bodies by oxidation; therefore, we need to counter then with anti-oxidants in our diet. People with CFS/ME have a particularly high need for anti-oxidants. Mine was climbing to the sky -- e.g. 'severe.'

Back in 2004, I checked my levels, found them moderately high, and explored numerous anti-oxidant products until I found one that worked. Taking Vibe, by Eniva, with its ORAC rating of 85,000 per ounce, was sufficient to bring my lipid peroxidation down to a safe level. Consequently, when Rich van Konynenberg told me I had to stop taking Vibe because of its folic acid content (400 mcg per ounce – the RDA), I was unhappy. Still I complied, and I felt my energy crash over the next few weeks, as I describe in the December 2008 posts to this blog.

Now I am worried. I can see that, even though I am taking products on this protocol to support the health of my cell membranes (the phosphatidyl serine complex and essential fatty acids), I am damaging those membrances faster than I can repair them.

I researched the antioxidants Yasko recommends, and put in an order. Now I am officially no longer on the simplifed five protocol, because my supplements include lots of Vit C, E, and Co Q 10, plus I've added grape seed extract and pycnogenol (anti-oxidants that help support GABA) and NADH to limit mitochondrial oxidation. I will most likely add some peroxynitrate scavengers from Martin Pall's protocol if my next test doesn't show a big reduction in MDA.

There is no doubt in my mind that a high level of lipid peroxidation is one of the reasons that PWC’s continue to deteriorate. (Others are the build-up of toxins, of chronic infections, and of nutritional deficiencies.) In the theory of natural healing, the body uses its vital healing force to repair the most recent damage before it gets around to repairing older problems. It is like going through the piles on your desk: last in, first out. In order to get to the bottom of the pile, you have to stop adding more papers to the pile. Similarly, to recover from CFS, we have to stop damaging our bodies.

This is another important reason why aerobic exercise should be avoided, giving preference to safer ways to increase circulation and maintain muscle tone. Aerobic exercise increases oxidative damage, especially in people with CFS.

Oxidative damage will [supposedly] reduce when the methylation cycle is finally working well, for reasons that involve a rather complicated biochemistry of five interlocking cycles in cellular metabolism – the methionine cycle, the folate cycle, the neruotransmitter cycle, the urea cycle, and the transulfuration pathway. In the meantime, we are wreaking havoc in our bodies. We need to reduce the continuing damage in every safe way we can, especially those of us who are over the hill (past 30), whose breakdown (catabolism) exceeds our rebuilding (anabolic) capacities.


Friday, March 13, 2009

Sulfate pathway under control

Hurray! My sulfate pathway in under control.

How do I know? I bought sulphate test strips and tested my urine. I’ve done the test twice so far.

The day the strips arrived, I rushed to the bathroom to urinate. I had been preparing myself for days to discover a high level so I wouldn't be disappointed. Both Dr. Roberts and Dr. Yasko advise their patients to follow a special supplement and dietary regimen for weeks or months, and I’d only been reducing protein seriously for a week!

I captured my urine in a plastic container, plunged the test strip in for a second, and stared at four little red squares. Red? The squares are supposed to be pink!

My first thought was, Suppose I am too high for the test? I couldn’t handle the suspense, so I walked away from the bathroom. A drink of water diverted me for a few minutes before I returned to study the test strip in daylight: there was 1 pinkish yellow and 3 pink squares.

When I compared my result with the pictures on the package, I saw that I fell into the category of >400. It wasn't the lowest category, and so I had to check my notes. Dr. Roberts asks his patients to get their levels to >400 and keep them there for two months. That's not too long to stay on this diet if I can keep getting encouraging feedback with my sulfate strips.

In case you haven't the foggiest idea what I am talking about, you can read the post preceding this one called "My pounding heart". Here's a quick summary. Starting at the methylation cycle where methionine is converted to homocysteine and then recycled back into methionine, some of the homocysteine binds with the CBS enzyme and is further broken down into glutathione and/or taurine. From there it is turned into sulfite, and finally into sulfate. (These chemical pathways have hundreds of steps, and I have only given the most important ones.) Problems arise when metabolites are moving too quickly down the pathway, leading to excitatory toxins like ammonia, hydrogen sulfide, alpha keto-glutarate, high sulfites, and high urinary sulfate excretion. Problems can also arise when something is too slow, for example, when sulfite is not being converted into sulfate quickly enough.

My urinary sulfate tested quite high back in April 2007even though I was functioning well and finally, for the first time in 7 years, had the energy to do aerobic exercise. I half-heartedly followed Dr. Amy Yasko's ammonia protocol, and then, because I didn't notice a difference, gave up on it.

When I started the simplified five protocol this past December, Rich van Konynenberg recommended the following changes:
A. Cut out supplements with high sulfur, such as N-acetyl-cysteine, whey protein powder, taurine, and glutathione.
B. Started the following supplements:
• Yucca (I sprinkle some on protein foods when I remember, or I take a pill)
• Activated charcoal (1x or 2x a week, I mix ¼ tsp with water and drink it down with a straw, always waiting 3-4 hours after my dinner-time supplements, just before going to sleep)
• Ora Kidney (a product from Douglas Labs) once a day with meals
• Molybdenum (I take the liquid E-lyte drops) to support the conversion (at the end of the pathway) of sulfite to sulfate

C. Make dietary changes. "No way," I told Rich at first "I have a freezer full of kale, collards, and other things from our garden; plus I love garlic and onions." But as I learned more, and thought about the benefits I got from making dietary changes in the past, I realized my resistance was foolish. When I read on Dr. Robert's site that his patients should get their sulfate levels down for two months and then can add back some of their favorite foods, I decided I could manage just about anything for two months. If I didn’t get results, I would go back to eating all my favorite, forbidden foods.

So here are the dreaded dietary changes recommended by Dr. Yasko. Reduce protein intake and reduce all high sulfur vegetables. Just about everything with protein in it has sulfur in it, which makes for a very limited diet. Dr. Roberts has detailed instructions with food lists and recipes.

However, there is one catch, and it's a big one: people with CFS/ME tend to have problems on a low protein diet. Our amino acids are always low, presumably because we are burning them for fuel, since our Kreb's cycle and mitochondria are producing insufficient energy through sugar and fat burning. I’m one of those non-vegetarian folks who withers like an old vine whenever I've tried a vegetarian diet. And should I mention that when I did the raw vegan experiment, the white light in my meditations turning into a bright red steak, pulling me out of meditation and into the kitchen.

My compromise diet is to take small portions of meat, fish, poultry, goat cheese or soy (about 2-3 oz at a time) and to select vegetables that are low in sulfur, such as lettuce, cucumber, carrots, celery, and beets. Before I used the first sulfate strip this past Monday, I also had dinners of beans and rice pasta. But I feel best when I eat low glycemic, unrefined carbohydrates.

Because of my first, good test result, while patting myself on the back for being virtuous, I decided to add a little more protein and sulfur to my diet and retest after 2-3 days. I had yummy collards one night for dinner, an egg two days in a row, and added some garlic to my gluten free pasta. Fortunately, when I retested urinary sulfate, I was still in the optimal >400 range!

But there is another twist: by adding more animal protein, my urinary ammonia went up. And this led me on a search to examine other pathways that make or process ammonia. My search led me to NOS (nitric oxide synthase), where I also have a genetic polymorphism (a nice way of saying a defective variation) that slows down the action of this enzyme. But that is another day's discussion!

What to do if you have, or think you could have, a sulfur issue
If you feel worse when you take high sulfur supplements like taurine, MSM, glucosamine sulfate... or antibiotics like Batrim... or if you’ve had reactions to sulfa drugs... or you have asthma, which is often associated with reactions to sulfites.... You could have a CBS upregulation or a slow BHMT enzyme.

Here are four ways to get confirmation of your hunch:
• order sulfate test strips from a chemical supply lab; for about $30, you will get a jar of litmus strips that can test for urinary sulfate. There are five possible test results. If more than one of the squares on your test strip is yellow, you’re excreting excess sulfate.
• do a laboratory test for urinary amino acids. If ammonia, taurine, and or cysteine are high (or if they are in a moderate range but quite high relative to other amino acids) you most likely will benefit from watching sulfur.
• do a laboratory test for urinary organic acids. If sulfate is high, you’ve been tagged.
• order the nutrigenomics methylation panel through This is the only certain way to know if you have a CBS upregulation or a BHMT downregulation.

I you decide to try the diet and supplement changes, here are a few caveats I've learned over the years.

Make everything you can from scratch, use organic and chem-free ingredients (locally grown where possible), and avoid restaurants. You can buy sulfite free wines and dried fruits at many health food stores.

Sulfites are in many processed foods. They are sprayed on light colored fruits and vegetables to prevent browning. Shrimp is sprayed to prevent black spots. Sulfites are also used to condition bread dough and to bleach food starches. Fortunately, a 1986 FDA ruling prevents their use at salad bars. All foods treated with sulfite must be labeled, so if you see a preservative on the list of ingredients, don’t buy that food. Restaurants that use canned and frozen foods most likely will have sulfites in their food.

See the FDA page on sulfite at

Another resource is the No Sulfites page where you will find several informative essays from an individual with sulfite intolerance.

It may seem impossible to spend more time in the kitchen if you already have limited energy from CFS/ME. But it will pay off in the long run. When I need to keep meals simple, due to limited energy, I have salad I’ve previously made up which I combine with a small amount of a protein source from last night’s dinner. I always make enough food at dinner to have at least one lunch from the leftovers. If I have leftover fish, I’ll mash it up like tuna salad, mixing in freshly chopped celery, or perhaps carrot and cucumber and some organic mayonnaise. Or I might slice leftover meat or chicken and make my own chef’s salad (without the highly preserved luncheon meats.) A good friend found me a breadmaker at a yard sale; now I make my own gluten-free bread from Bob’s Red Mill mixes. His GF brown bread is delicious, and I spruce up the GF sandwich bread mix with fresh herbs, or poppy and caraway seeds, or sunflower and sesame seeds. I even made it once with pitted black olives. Yum!

Thursday, March 5, 2009

My pounding heart

My heart pounds, blub blum blub blum, as I lie in bed with closed eyes. A few minutes ago it seemed normal, quietly doing its job while I went about mine. Now its beat is loud, annoying, demanding, incessant. Listen to me, listen to me. I get out of bed.

Almost everyone I know with CFS deals with this pounding heart, and none of our doctors have any idea what is causing it. Nor do they know how to stop it. I’ve noticed over the years the things that often ameliorate it:

• doing yoga inversions, especially supported shoulderstand.
• doing a few vigorous yoga poses, like upward facing bow (a backbend – not recommended for beginners) that open the hips and the chest
• eating plain yogurt or goat cheese

This weekend I clicked on the link to a website written by a cardiologist who has been familiarizing himself with Dr. Yasko’s research on methylation defects in chronic and understands how to explain it. In reading over Dr James Roberts discussion of methyl cycle genomics in heart disease, I suddenly had an aha! moment. I understood how my own methylation genetics have created Pounding Heart at Rest.

Over the last few days I’ve been working to wrap my mind around these ideas. Here’s what I’ve come up with.

A pounding heart is a normal reaction to vigorous activity such as running. The demand (stress) of movement stimulates the SNS [sympathetic nervous system] to release adrenaline and noradrenaline (or if you prefer the British terms, epinephrine and norepinephrine) as well as the hormone cortisol. When the activity stops, the heart rate slows and soon returns to normal as the PNS [parasympathetic nervous system] brings the body back to homeostasis.

Certain methylation cycle defects lead to excess stimulatory activity and insufficient inhibitory recovery, and I have just about all of them. The main culprit is CBS – not the television station (even though watching TV late at night is rather stimulatory) -- but an enzyme known by that name whose job is to funnel metabolites of the methylation cycle out of the system. Meet Cystathionine Beta Synthase, a hardworking supporter whose job is to funnel homocysteine into cystathione so that the next enzyme can make cysteine and alpha keto glutarate (AKG) both of which are used for other important things. My CBS is overly enthusiastic due to a certain genetic variant known as a SNP or polymorphism. This simply means that one of the normal amino acids on the gene has been replaced by a different one, and this can happen in all of the genes if you are (CBS +/+) or half of the genes if you are (CBS +/-). I happen to have the latter variant, half of my genes. I also have other variations further upstream that intensify the imbalance.

Imagine CBS as a worker on an assembly line. If she does her job five or ten times faster than everyone else, a bottleneck will develop and then trouble will result. The enzyme that is supposed to pick up some homocysteine for recyling before CBS grabs it must also works overtime. Unfortunately, this enzyme, called BHMT, has just the opposite genetic variant in my body: it works more slowly. The net result is that my enthusiastic CBS makes lots more cystathionine than it should.

This has multiple effects. Upstream, there is not enough homocysteine getting recycled back into methionine so that it can be used to make SAMe which can then be used to make DNA, RNA, protein, lipids, creatine and creatinine. Hence, on lab tests, homocysteine, methionine, SAME, and creatinine are low, and I crave red meat whenever I try vegetarian diets.

But the downstream effects are worse, many times worse. Here’s what Dr. Roberts has to say:
The 10-fold up regulation in CBS generates sulfur breakdown products (sulfite and sulfate, which stimulate the stress/cortisol “fight or flight” response), excess ammonia (in the process wasting BH4 which is used up detoxifying ammonia), hydrogen sulfide (producing “brain fog”), and alpha-keto glutarate (leading to “excitotoxicity”). The G6PDH enzyme system may be affected, leading to abnormalities in sugar control. Methylation intermediates will “fall through this drain”, so the entire system suffers; our defenses against viral invasion and toxicity suffer. Co-Q10 and Carnitine generation will fall off due to impaired methylation, and ATP levels fall, robbing you of energy.

If this is all you want to know, skip to the end. If you want more details, read on:

1. The excess cystathionine is converted to cysteine and alpha keto glutarate (AKG). AKG is excitatory; when there is too much, the inhibitory GABA (the receptors that Valium binds) can’t operate properly to balance the excitation.

2. If this weren’t enough trouble, a byproduct of the conversion is ammonia – that stinky stuff used in oven cleaner, Phew!, toxic even in small amounts.

3. Of course the body has ways to detoxify ammonia. But in doing so, it uses up a very important enzyme known as BH4. BH4 makes non-toxic byproducts from ammonia and arginine, and helps us make the important feel-good neurotransmitters dopamine and serotonin. When BH4 stores are low, instead of getting non-toxic byproducts, we get lots of free radicals (peroxynitrite and superoxide) that go about damaging cell membranes until they are neutralized by anti-oxidants. And mood disorders can result because there isn’t enough BH4 to make all the right amounts of feel-good neurotransitters.

4. The excess cysteine gets converted to taurine rather than to glutathione. The lack of glutathione impacts the function of the immune system and lowers the ability of the body to detoxify heavy metals.

5. The abundance of taurine is less problematic, for taurine has lots of good uses in the body. It is important in the visual pathways, for the brain and nervous system, and for cardiac function. It facilitates the passage of sodium and potassium ions into and out of cells, electrically stabilizes the cell membranes, and functions as an inhibitory (calming) neurotransmitter. It conjugates bile acids for efficent fat absorption & solubilization. Not bad for one amino acid.

6. A byproduct of the conversion to cysteine and taurine is hydrogen sulfite, also known as the brain fog molecule, the one responsible for the foul smell of farts and cooked hard-boiled eggs. Here’s what a Wikipedia article says about the toxicity of hydrogen sulfide (H2S)
a broad-spectrum poison ... although the nervous system is most affected...which forms a complex bond with iron in the mitochondrial cytochrome enzymes, thereby blocking oxygen from binding and stopping cellular respiration. Since hydrogen sulfide occurs naturally in the environment and the gut, enzymes exist in the body capable of detoxifying it by oxidation to (harmless) sulfate.

HBOT (hyperbaric oxygen therapy) is particularly efficient in helping remove toxic hydrogen sulfide, which is why most people with CFS have a positive response to this therapy, but also why it doesn’t last: we have not been poisoned by breathing exogenous H2S but rather by our own excessive production of it.

In the body, H2S acts as a vasodilator (which can explain the prevalence of orthostatic intolerance in people with excessive H2S production) and in the brain increases the response of the NMDA receptor (which Martin Pall has shown is responsible for chemical hypersensitivity in those of us with CFS and MCS.)

7. And if all this isn’t enough, we get lots of neurotoxic sulfite, which overwhelms the SUOX enzyme that uses molybdenum to convert it into the less toxic sulfate.

8. Even if we support the SUOX enzyme into converting sulfite to sulfate, we have an abundance of sulfate, which stimulates the fight, flight, freeze response. We produce SNS neurotransmitters adrenaline and noradrenaline as well as cortisol, until the adrenals get too exhausted to produce high amounts of cortisol. All these stress hormones lead to a pounding heart.

Do you have sensitivity to sulphur products: sulpha-drugs, foods high in sulfur, or sulfites added to wine and dried fruits? Leave a comment below.