Friday, February 27, 2009

Ribose or comatose

Nearly comatose with fatigue last week, an article crossed my desk entitled “D-ribose, chronic fatigue and fibromyalgia.” The author, Tori Hudson, is a noted naturopath, a clinical professor, and director of a medical clinic dedicated to women’s health. She writes: “I have found D-ribose to be the single most important nutrient in the search for alleviation of symptoms and a path towards heath.”

Why did I stop taking ribose? I try to recall when I tried it. It was shortly after Jacob Teitelbaum published his pilot study in November 2006 J. Altern Complement Med I read a short summary of the research in The Townsend Letter, where Teitelbaum wrote a monthly column, and decided to order it. Perhaps because I was already taking a small dose in Vibe, or perhaps because I was on the downhill slope of a miserable relapse, I didn’t notice any difference. When I used up the second container, I didn’t reorder. Then I forgot all about it.

Now I’m pulled back to read more carefully. My attention settles on a summary of laboratory findings of deficiencies. Apparently, those of us with CFS have been found to have
• 20% less energy in our muscles. Yup, I feel this every time I go to the gym.
• defective or inefficient mitochondria. Hmmm, the mitochondria are the energy factories of each cell, so that makes sense.
• nutrient deficiencies in cells and tissues needed to process food into energy. Like what? Magnesium? B vitamins?
• thickened capillary walls slowing the rate of energy synthesis.

There is no citation for the last claim, so I get curious. And soon I am on an internet search.

What I want to understand is: what does ribose have to do with any of this? I already know ribose is a component of ATP, the substance needed by every cell in the body to produce energy for its function. I also know ribose is a component of RNA, whose full name, ribo-nucleic-acid, lets us know it contains ribo(se). RNA, in case you slept during high school biology, is needed by the body to make DNA, which is needed every time a cell duplicates or repairs itself – an activity happening a million times a day. I also learn that ribose is in NADH, a rather expensive supplement I’ve tried before physical exercise. The box advertises that it improves cellular energy & elevates mental clarity – cell regeneration – DNA repair – boosts immune system – a potent antioxidant. Anything that can do all that has to be good. Right? Fourth, ribose forms part of Coenzyme-A, which is needed to run the Krebs cycle where fat is burned for energy. A Wikipedia article informs that Coenzyme A helps transfer fatty acids from the cytoplasm to the mitochondria. Coenzyme A is made from panthothenate, also known as vitamin B5, which is an important nutrient for adrenal function. So many things work together.

I wonder if ribose has any relationship to the glutathione - methylation cycle. Could it screw up the Simplified Five protocol in which I have already invested three months of time.

There is some old discussion about ribose on the Yahoo group, Yasko CFS_Experimental, where it is grouped with other supplements that support mitochondrial activity. Rich van Konynenberg contributed his opinion that lowered mitochondrial activity could be one way the body protects itself; that this symptom from which we PWC's suffer is a compensation against excessive oxidative stress. Taking things to increase mitochondrial activity, he warns, could increase oxidative stress, further damage cell membranes, and ultimately make the body worse. But Dr. Amy Yasko recommends Beyond C with ribose as appropriate supplementation for many genetic profiles, as well as other supplements that support healthy mitochondrial activity. (See p 148 ff of Genetic Bypass).

Despite having parted with a year’s worth of massage money to consult with Rich, I’m not ready to listen to him. Perhaps it is hubris, perhaps skepticism, perhaps sheer desperation to get past this near comatose stage of my healing journey. I order a jar of d-ribose on Wednesday. Then I read more.

Normally ribose is formed in each cell through a process of bio-chemical reactions known as PPP (pentose phosphate pathway). This pathway also helps to make a very important substance called NADPH (nictinamide adenine dinucleotide phosphate) which the body uses to convert the bad, oxidized form of glutathione to the good, reduced form of glutathione. Both forms of glutathione are measured in the methylation panel. Reduced glutathione is good because it removes peroxides from the system, hopefully before they can damage cell membranes. The red blood cells are really good at this; but heart and muscle cells are not as well equipped to do this because they lack certain enzymes. They like to use glucose for fuel, and so let ribose stores get low. Hence, it takes a while to recover when we work our heart and our muscles hard.

People with CFS presumably get caught in a vicious cycle. When ribose gets low, ATP gets low, and reduced glutathione gets low. This does not make for happy cells but rather cells as stressed out as a peri-menopausal woman with PMS on a 1000 calorie diet. They look at all the ADP which has accumulated, and wishing they could make it into ATP, but can’t, they go bonkers; they break down the excess ADP and throw out the nucleotides and the purines. Ha! Then they sigh and take a rest. That’s all they can do now. Gees! You’d think they’d know better. But it’s not as if they can reason. They do what is necessary to maintain balance, which means recovering a certain, normal ratio of ATP to ADP.

So the theory is: give the body abundant ribose so it has the stuff available when it needs it. Maybe, if you’re lucky, it will make more nucleotides and rebuild ATP stores; then it can rebuild glutathione. It’s a long shot, perhaps, since we all know that rebuilding glutathione depends upon proper methylation. But the good news is that taking extra ribose isn't likely to send the mitochondria on an energy-producing binge only to leave us with the Mack-truck-hit-me hangover the next day from unrepaired oxidative stress.

Teitelbaum's study found that 66% of the patient with CFS and Fibromyalgia who took 5 gms (1 small scoop) of ribose three times a day for about three weeks showed a significant improvement in energy, sleep, mental clarity, pain, or general well-being. Nearly half had a significant increase in energy.

I’ve been taking ribose for a week, and I’m glad to report that I have increased energy, increased mental clarity, and increased well-being. I no longer fell comatose. Yeah! I suspect that once I replenish the ribose stores, my improvement will plateau. I’m not sure I’ll even need to continue taking it. But for now, I’m grateful to the researchers and clinicians who decided to explore whether ribose could help people with CFS.

Have you tried d-ribose? What results did you get? Leave a comment by clicking on the word "comments" below.

Friday, February 20, 2009

On Gratitude (But Be Careful What You Wish For)

Full of gratitude last night, I celebrated a Hindu holiday called Mahashivaratri by eating an Indian dinner and then chanting with a group of friends. Just before the chant I chose a wish card from the dish at the entrance to our chanting and meditation center: “Prayer”. Good, I thought, I want to remember to pray for my friend’s husband who just went through a grueling surgery. During the chant I found myself offering blessings — an especially Jewish approach to prayer in which we praise the Creator before every action (waking, dressing, lighting candles, eating). After the chant I found myself praying in a more Western/American way, asking to experience gratitude all the time, even for all the humdrum things I take for granted.

Guess what? My prayer was answered, but not in the way I thought and hoped it would. Instead, I was given experiences that enabled me to more clearly see what I have to be grateful for. I thought constant gratitude might be like infatuation: walking around with a silly smile and a big open heart. Perhaps I am just at the early stage, like getting a crush on God and the Universe before it escalates to the point of infatuation.

As I sit here writing at 5:00 am after a sleepless night, I remember how I used to wish I could pull all-nighters to get more books and articles written. Sleep seemed like such a waste of time in those days of being a busy art historian. At night the world is quiet and the phone never rings.

Ah, I must be careful what I wish for.

Insomnia dropped in with the speed of a Comet, no warning until I got into bed at 11:30, tired but not sleepy. A half hour later, I was no closer to falling asleep. I had felt good all day; now all of a sudden my heart was pounding as forcefully as if I’d just climbed a steep hill. Neither a homeopathic nor a pharmaceutical sleep aid made a smidgen of difference –one of the more perplexing symptoms of CFS. Eventually I got out of bed to surf the internet and write.

The experience makes me realize how lucky I have been! Last year, I had nights like this every week, often twice a week. This is the first time in two months I’ve had to go through it again (the last when I tried supplemental SAMe – see post, SAMe is not my friend). That is something to be grateful for!

Earlier in the week I had another recollection of the past and another opportunity to count my blessings. I missed my nap Friday to join a group of poets for a luncheon followed by a session of critiquing. I got home after 5:00 pm, exhausted, eyelids propped open with toothpicks until an early bedtime. The next morning I was in a black fog --bitter, irritable, and depressed enough to wish I could go to sleep and never wake up. What a sorry Valentine I was for dear David!

Two things helped me through it: the knowledge that I used to be this way all the time in 1994 and in 2000 (nadars of this illness from previous relapses), and the certainty that all this would eventually pass. Looking back, I am so grateful that my moods are now generally stable. Apparently I have learned to care for myself in ways that usually keep them so.

When a long afternoon nap and a gentle session of hatha yoga failed to turn my mood, I took desperate action. I didn’t want to go our for a romantic Valentine’s Day dinner like this! I remember that mood disorders are often gastrointestinally based. Here is some evidence:

1. Gut bacteria release toxins result in depression. See this recent medical abstract The gut-brain barrier in major depression: intestinal mucosal dysfunction with an increased translocation of LPS from gram negative enterobacteria (leaky gut) plays a role in the inflammatory pathophysiology of depression.
2. Research suggests that bacteria in the GI tract can communicate with the central nervous system, even in the absence of an immune response. See this medical abstract: Major depressive disorder: probiotics may be an adjuvant therapy
3. Michael Gershon, a Professor of Anatomy and Cell Biology at Columbia University, called the enteric nervous system “The Second Brain.” His groundbreaking research deals with the complexity of the enteric nervous system, the role of gut neurotransmittes like serotonin (80% of the body total amount in the gut), and the connections between gut and brain, instinct and mood. His book is available online.

Naturopaths have been making these claims for decades based upon clinical experience: give a depressed patient a colonic and s/he feels better. So, being the good naturopath that I am, I give myself a coffee enema: two tablespoons of brewed organic coffee in about two cups of water. I use coffee because it is known to increase glutathione, a potent anti-oxidant that supports detoxification. Voila! After the enema I feel much better We’re a little late meeting our friends because I have to run back to the bathroom, but they don’t mind. They’re even later.

Does all this have anything to do with methylation? Does it affect mood? You bet. Stay tuned for the next post.

Wednesday, February 11, 2009

How to Get Started on the Simplified Five

My friend Bonnie, with Lyme-induced CFS, is intriqued by the methylation protocol. But she is confused about how to get started. So I am dedicating this post to her (and to all of you out there whose cognitive abilities have been damaged by this illness.)

A little history. And why not? I’m an historian

The first group of protocols to address methylation cycle issues was developed by Dr. Amy Yasko. Working with autistic children, she found that by correcting methylation imbalances, she could start turning these kids around. She also began testing for genetic variations. This way she could individualize treatment and understand why some kids got worse on the same product that helped others improve. Her protocols became increasingly complicated, with lists of over 100 supplements to try and with loads of expensive tests to take regularly to monitor progress.

Rich to the rescue. He noticed that many mothers of kids with autism had CFS. I happen to be one of them. My daughter, Lisa, was born with infantile autism, although she was not diagnosed as autistic until age 3 (in 1982). As the autism spectrum disorder became subdivided, Lisa’s diagnosis was changed to PDD (pervasive developmental disorder). Another friend of mine with a bad case of a dysautonomia known as POTS (which overlaps with CFS – see my post from January 5, 2009 titled My two most disabling symptoms) has two boys with Asperger’s. I realize this isn’t a scientific sample... But hey, when we understand things in terms of our own experience, it sticks.

Rich began to investigate the CFS-autism spectrum connection. On a yahoo discussion group known as CFS Experimental, he suggested that people with CFS start following the Yasko protocols. Some of us tried. We purchased her books and DVD lectures. We did the tests. We bitched online about how complicated it all was, how we couldn’t understand it. A few rookies read everything and became ‘experts’ on the Yasko protocol. I backed off in frustration because I developed a major eye problem – a macular hole and retinal detachment with a possible loss of vision – and had to go into surgery. The next year I had five eye surgeries. And when I came back to Yasko, I found that Rich had come to our rescue. He had been reading our posts, corresponding with many of us, and looking over our test results. He decided to boil down the whole complicated mess into five basic supplements. He put forth his ideas and invited people to try them.

Here is Rich’s basic simplified five supplements:
1. ¼ Folapro (made by Metagenics)
2. ¼ Intrinsi B12/Folate (made by Metagenics)
3. 1 or 2 HHC Neurological Health Formula
note: Rich recommends sensitive individuals start with ¼ and work up
4. 1 or 2 Phosphatidyl Serine complex (from Vitamin Discount Center)
5. 1 or more sublingual hydroxycobalamin tablets (Perque Activated B12 Guard)

What is in these supplements? What makes them special? Folapro is a form of the active folate in the methylation cycle called L-5-methyl-tetrahydrofolate (abbreviated 5-methyl-THF). Intrinsi B 12/folate contains a mixture of two active forms of folate (more 5-MTHF and some 5-formyl-tetrahydrofolate, which is apparently very difficult to find), a little folic acid, some inexpensive cyanocobalamin (the normal form of B12) and some intrinsic factor (which helps the body use B12). Neurological Health Formula is a multi vitamin specially formulated by Dr. Amy Yasko for her patients. Phosphatidyl Serine complex has the normal mix of phosphoralyted serine, choline, ethanolamine, but it also has some plant-based essential fatty acids such as GLA and LA from flax oil. Perque Activated B12 is the highest dose (200 mcg) and least expensive sublingual hydroxycobalamin around.

Variations on the Simplified Five
A little internet research shows that Metagenics also sells a product called ActiFolate which contains the same 3 folates that are in Intinsi-B12/Folate (800 mcg of combined folic acid, 5-methyl-THF and 5-formyl-THF) but doesn’t include the B12 or the intrinsic factor. Dr. Sara Myhill in the UK has picked up Rich’s idea and devised her own simplified five protocol.
She recommends
• Hydroxycobalamin 5,000 mcgms daily (or cyanocobalimin "shot O B12")
• Methylcobalamin 1mg sublingually
• Methyltetrahydrofolate 800mg (ActiFolate)
• Pyridoxal 5 phosphate 100mgs (50mgs twice daily)
• Glutathione 250mgs daily
• Phosphatidyl Serine 200mgs (100mgs twice daily) – BioCare
Note that Dr. Myhill’s protocol doesn’t include any intrinsic factor. The dosages of folates, B12, and methyl donors are significantly higher. Her protocol also includes pyridoxal 5 phosphate, the active form of Vitamin B6 and oral glutathione.

There is some debate as to whether P5P is really necessary. (See the research summary by Mark Kaye at Metagenics arguing that it is not, and the research summary by Ray Sahelian arguing that some individuals do not make the conversion due to their genetics.) As far as I know, people with chronic fatigue have not been widely tested for this genetic variation. Several individuals on the Yahoo Yasko group have suggested that the presence of heavy metals blocks their conversion of B6 to P5P, so they do better taking the active P5P form.

In Rich’s simplified five protocol, the Neurological Health Formula includes 2.1 mg per tablet of B6 in the active form of P5P. The RDA for B6 is 2 mg a day; the safe upper limit is 100 mg a day; toxicity in the form of reversible nerve damage can occur at doses of 250 mg a day. I’ll talk more about B6 in a future post.

If you decide to start the Simplified Five protocol, you might want to get a baseline of how your methylation is working. The most thorough test is a methylation panel ordered through Vitamin Diagnostics Inc, a receiving lab in New Jersey that works with a Dutch company that actually does the testing. (Yes, they send your blood over to the Netherlands, so it takes 1-2 months to get back the results.) The cost is $300 and must be ordered by a licensed physician.

After testing, introduce the supplements slowly, working up to the recommended dosages. Start the B 12 after you’ve started all the other supplements. Don’t take extra sources of folic acid (Read labels on foods and vitamin pills).

You might want to contact Rich Van Konynenberg to share your methylation panel test results and your experience with his protocol. Happy pill popping!

Tuesday, February 3, 2009

Great! I have a headache

Great! I have a headache.

OK, I could be talking in a sarcastic tone, but I'm not. Seriously folks, I'm actually glad. Not that I'm enjoying the feeling of having a headache... (If that were the case, you could check me into St. Elizabeth's right now!) No, I'm glad because headaches are a sign of detox.

If you've been following my posts, you'll know that I've been on the lookout for signs of detox. Rich van Konynenberg told me to expect some sign of detox. It would be a sign that the treatment is working.

How do I know this is detox and not a random headache? First of all, I rarely get headaches -- maybe one or two a year at most. Second, I've noticed a pattern of mild headaches on and off all week. Third, these headaches don't feel like normal headaches and their location keeps moving around. More significant is that these symptoms have followed periods of great energy, that my energy level has almost returned to what it was before I started this protocol, and that my symptoms of dysautonomia have abated.

Why is this significant? The pattern, according to the theory of natural healing, is a sign that the body is healing. I learned this theory in naturopathy and homeopathy classes as well as from the experience of working with ARL Research Labs.

A weakened body puts its limited energy into maintaining itself. As it begins to heal, as metabolic processes, hormones, neurotransmitters, and organ functions rise in efficiency, an individual begins to experience increased well-being. But this beloved and delightful increase is short-lived because the body now has the energy to start eliminating stored toxins. These toxins have contributed to the state of ill health, and typically include viral and bacteria particles, heavy metals, plastics, pesticides, excess metabolites from vitamin supplements or pharmaceutical drugs. As these substances are released, the detoxification pathways become loaded, and the individual feels worse again. But unless the detox is excessive, the body is able to eliminate the increased load in a few days. Then the cycle repeats itself, building up to increased well-being and ending with detox symptoms.

Rich thought the high level of folic acid (methylation panel results) will need to be detoxed. High folic acid creates a functional B-12 deficiency. It can also (according to Rich) interfere with proper folate metabolism. Folate is the active, natural form in the body.

A lack of adequate folate can lead to:
Digestive disorders such as diarrhea
Loss of appetite
Weight loss
Sore tongue
Heart palpitations
Behavioral disorders
Elevated homocysteine

(Note: this information comes from the NIH Office of Dietary Supplements)

From the same site is the following discussion:
What is the health risk of too much folic acid?
Folate intake from food is not associated with any health risk. The risk of toxicity from folic acid intake from supplements and/or fortified foods is also low [65]. It is a water soluble vitamin, so any excess intake is usually excreted in urine. There is some evidence that high levels of folic acid can provoke seizures in patients taking anti-convulsant medications [1]. Anyone taking such medications should consult with a medical doctor before taking a folic acid supplement.

The Institute of Medicine has established a tolerable upper intake level (UL) for folate from fortified foods or supplements (i.e. folic acid) for ages one and above. Intakes above this level increase the risk of adverse health effects. In adults, supplemental folic acid should not exceed the UL to prevent folic acid from triggering symptoms of vitamin B12 deficiency [10]. It is important to recognize that the UL refers to the amount of synthetic folate (i.e. folic acid) being consumed per day from fortified foods and/or supplements. There is no health risk, and no UL, for natural sources of folate found in food. Table 4 lists the Upper Intake Levels (UL) for folate, in micrograms (μg), for children and adults.

Since I don't eat foods fortified with folic acid (mostly those made with wheat flour), and since the supplement (Vibe) I was taking kept me within the reference range, I want to reevaluate the reason for the high level of folic acid on the methylation panel. Could it reflect the amount I took the previous day? Or does it reflect an inability to eliminate excess folic acid?

Rich van Konynenberg wrote:
High values [of folic acid on a methylation panel] are sometimes associated with inability to convert folic acid into other forms of folate, because of polymorphisms in the DHFR [dinydrofolate reductase] enzyme.

DHFR is the enzyme that catalyzes the conversion of folic acid into THF [tetrahydrofolate], a crucial step in the methylation process. Although I tested for various genetic polymorphisms associated with methylation, DHFR was not one of those tested.

Still so many puzzles to solve.... It is as if we are setting out on a long journey and don't know where we'll end up.
By the way, for the last week, I've continued with two hydroxy B-12. One day, I tried three of those tablets, but it adversely affected my sleep. I woke many times during the night and early in the morning. But I learned something important: the extra hydroxy B-12 had the same insomniac impact on me as did the extra methyl B-12 and the SAMe (see my previous posts "SAMe is not my friend" and "The blue vitamin: B-12)adding to the puzzle of what causes what.