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Monday, December 15, 2008

Vitamin D redux

Sometimes you do a better job when you don't know what you are doing. As I started treating Lyme disease my mentor told me that vitamin D was low. It should be checked and replaced. I dutifully checked vitamin D OH 25 and found it to be uniformly low. I immediately started new Lyme patients on high dose pulses of vitamin D. In retrospect they all did well with this approach. Then I learned I wasn't supposed to do this. The patients were vitamin D toxic. When I checked vitamin D dihydroxy 1,25- the active form,I found that sure enough, the patients were really vitamin D toxic! Now I told my patients to withhold D and even consider Benicar. This was based on theory- not practice.

What if I was right the first time?

One huge problem with Lyme patients is that they don't make antibodies against the germ. In technical terms there is a poor humoral response.

What have we (I) learned? Lyme is a Th1 disease associated with a shift away from Th2. This describes a helper T lymphocyte response. (If you don't know what that means you can still follow the gist of this blog). The Th2 response is needed to promote antibody production. These Th1 weighted patients need a push in the Th2 direction to gear up the antibody making machinery. Vitamin D helps with this according to my immunology text.

Maybe high/toxic vitamin D levels are a good thing. Maybe they help (in lingo) up- regulate immunological receptors which would increase antibody production, a major thing that is missing in Lyme patients!

Maybe it is particularly useful to give extra D when antibiotics are first prescribed and a Herx occurs. This might be a critical chance to influence ongoing and future production of antibodies directed against Lyme.

All of the above is wild speculation and based on a logical argument which may be filled with flaws. Really the point is we don't know what we are doing with vitamin D; and, how did a theory from a non physician, about a disease other than Lyme disease, become so influential amongst LLMDS and the Lyme community at large?


dogdoc said...

Hi Doc. Hate to burst your newly formed Th1 bubble. Much of immune response to Lyme was initially studied with convenient Lyme arthritis model and the reaction was considered to be a Th1 disease. However, the arthritis guys are now questioning the vailidity of there Th1 assumptions, for many reasons including IFNgamma is not required for the response. There is an excellent review in "Lyme Arthritis: Current Concepts and a Change in Paradigm" Nardelli, et al Clin Vacc Immunol 2008 January; 15 (1) : 21-34. In addition, there is mounting evidence that in chronic neuroloborreliosis, a Th1 response is associated with successful outcome and the chronic stage is associated with a Th2 response overall. There are quite a number of references here- none as comprehensive. A couple of good places to start- "Borrelia burgdorferi- Induced Tolerance as a model of Persistance via Immunosuppression" Diterich et al. Infect Immun 2003 July; 71(7) 3979-3987 has some review info also. This one does as well- its a mouthful of a title but not as bad in its discussions. "Decreased Up Regulation of the Interleukin-12 R beta @- chain and Interferon gamma secretion and Increased Number of Forkhead Box P3- expressing cells in Patients with History of Chronic Lyme Borreliosis Compared to Assyptomatic Borrelia exposed Individuals" Jaretors, et al. Clin Exp Immunol 2007 January; 147(1) : 18-27. There are many others- won't fill up space in your blog. It seems that early Lyme patients follow Th1 response as in the standard lyme research model (arthritis that is). However, in humans, not mice arthritis models, the responses change when going from acute responses to chronic responses and that Lyme here is not a simple straightforward Th1 disease as once assummed. Gotta watch those rheumatologists again- they put a lot of tunnel vision into current ways of thinking.

dogdoc said...

On Vitamen D- thats a huge subject unto itself. VDR's (vitamen D receptors) are involved heavily in immune signaling accross the board in all aspects of cellular and humoral immunity. They are more a universal hormonal messenger in immunity when it comes down to it, as apposed to being for or against anything specific. Your inital observations are apt- as are Marshalls- in that chronic patients do have high active levels of Vit D and conversely often low levels of inactive vit d. This is assumed to be associated with vit d activation in immune cells at the cellular level when reacting to intercellular bacteria. This indeed does happen in the test tube. However, I at least have not found the clinical application research to back either position. Ancedotally patients are "helped" by alternative approaches but none in double blinded studies. The basic research that is out there does not support a simple application of either vitamen D supplementation or avoidance. In addition, there is little to show what the true state in the body actually is- is the active Vit D excess or the inactive Vit d lesser amount indicative of the bodies needs? In most other disease, we go by active state of hormones. We also have no evidence to show us one pool affects the other- that is we supplement or reduce the inactive pool that it will in anyway effect the active pool being produced at the cellular level. It is being produced at the cellular level as an immune response- because there is more inactive precursor doesn't mean that immune response will be driven in that direction. It is antigen driven. But there are huge numbers of VDR's throughout the system all doing divergent signaling activities. Focusing a treatment on only the basis of one of those small parts of the system doesn't make sense. Any more than it does to make blanket statements about any other steriod whose receptors are present throughout the immune system- glucocorticoids, androgens, ect. Supplementation with any of these makes patients feel better as well. As well as reduces Th1 responses I might add. However, what does the chronic Lyme patient need to get rid of the organism? In terms of Vitamen D, I beleive the verdict is still unknown.

Eric said...

To bad there's no simple way to track OH 25 vs. 1,25D ... all I know is that I felt dramatically better after a few days of Hawaian Sun recently (with the benefits persisting for 3-4 days after returning).

Less stress? maybe, but I was working hard while there.

Immune down regulation and thus less inflamation from excess 1,25D? Counter-intuitive, but maybe.

Anyone really believe the Marshall protocol works?

Bryan Rosner said...

The most convincing part about the marshall protocol for me was the results. There seem to be patients who don't get results, but for those who do, the results are often dramatic. For me it was life-changing results. When I found others who experienced the same, it was more convincing. As for the sciences...I'm not sure.

Seems different individuals may respond to different treatments.

Unknown said...

First off, thank you for this blog. I appreciate being able to read your thoughts about tick borne diseases. Typically, I am a lurker. But I would like to relate the experience of 5 people in our local support group that did the Marshall Protocol for at least 5 months, some longer.

I do not want to start an anti Marshall Protocol campaign. But my observations of 5 Lyme patients taking high dose Benicar, (including my son), was that the protocol was worse than the disease. It gave new meaning to the word suffering.

Yes, there are people who do well on Benicar. But it is a small subset. The rest have a decrease in quality of life. And many go into what we named a "perma-herx".
The symptoms being an incredible depression that they could not pull out of for weeks or being bedridden for weeks when they used to at least be able to be upright and ambulatory.

These 5 went on to use the Schardt protocol: Diflucan and Penicillin. It was more tolerated and many saw an increase in their quality of life. One person returned to work part time. Another returned to full time work.

For this small group of people the Benicar and Vit D avoidance was not successful and definitely detrimental.

dogdoc said...

I think Bryan has a good point about individuals responding to different treatments. It may have to do with whether your particular body has the tendency to run to the autoimmune or to the immunosuppressed ends of the spectrum. Genetic tendencies we know are involved here. In addition, what additional infections that have been picked up or reactivated in the indidividual may be a factor as well.
I'm probably going to get lynched for this one- but Bryan, I'm glad we did not scare you off. I think everyones comments and experiences are important.

Michele said...

On Vit D; My doc did not recommend it. I looked at the consequences of what very low Vit D could cause (mine was very low) and just decided that the consequences of letting it remain very low were not worth the risks(although I never found any literature on the risks of taking the supplement if you have Lymes). There did not seem to be any consensus in the Lyme community about vit D so I took the supplements and felt better. That was how I made my decision and the logic might not make medical sense but that was the logic I used.

Unknown said...

I have been supplementing with Vit D3 for over 18 months at approximately 5,000 IU daily in the winter. The improvement in my symptoms was nothing short of astounding - I have had Lyme disease for over 20 years. It is food for thought that Vit D has been very effective in mitigating the impact of MS - which I personally believe to be an illness of bacterial origin.

pjeanneus said...

I tried the Marshall Protocol for 15 months. I found no change at all, but then I had been on antibiotics for several years and was somewhat recovered, not completely. My D levels at the start were 20 and 40. My D levels after many months without any D were 18 and 38. I saw patients on the message board with D levels which both dropped below 20. I was afraid they would get cancer. My hunch is that early on with chronic inflammation the 25 D is rapidly converted to 1,25 D and then, over time, there is burn out leaving insufficient 1,25 D.

I liked the Marshall Protocol to begin with because I think he selected the safest and most effective antibiotics, Zithromax, minocycline and then a couple of others. He also used them low dose and pulsed which probably fools the borrelia into coming out of hiding. Furthermore, the Zithromax and minocycline had been very effective for me over time. I have borrelia and mycoplasma, and probably a few other infections.

I challenged Dr. Marshall that calling cfs or Lyme a Th1 disease is confusing as cfs has been defined as a Th 2 shift where the immune system is overactive but can't get at the germ. This would fit with the concept that the low dose, pulsed approach is what works NOT the reduction of D.

Over time, some MP patients have relapsed and become very sick again. Some seem to have done well. Personally I think the high doses of Benicar and abnormal, severe reduction of D are intutively not good for human beings.

I currently take 5,000 u of vitamin D 3. It's too early to tell if this will help me.

Unknown said...


I am not sure yet if I have Lyme . . I am still in the process of a work-up, but was found to have Vitamin D levels below 20 according to both markers. I have been afraid to supplement due to the confusing information I have found regarding Vitamin D supplementation and tick-borne illness. After reading this I just took the supplement. Hope I'm making a good decision. I can't afford ot feel any worse. I was also at the low end of B12, low in Folic Acid and mildly Anemic so am taking a multivit with iron, B12 and iron every other day. I am unclear about the appropriate dose of D!

Shawn B. said...

This page is a goldmine for putting the claims of the Marshall Protocol in scientific perspective. Someone at MIT sat down and debunked the living you-know-what out of the MP, with reference after reference after reference:

Unknown said...

Wow. That is quite a rigorous (and damning) examination of the Marshall Protocol. Thanks for sharing.

LimeEone said...

I am another chronic Lyme patient who tried the Marshall Protocol. I ended up much worse than when I started, and now, over a year after stopping, I have not returned to baseline.

A previous poster said, a perma-herx sets in -- this is sort of what happened to me, though I think there was something other than bug-killing causing my awful decline. And by decline, I mean going from semi-functional (at a very low level -- able to take care of myself, though) to completely disabled. I was in bed a whole year, too weak to do the most basic human chores. It was a nightmare. Now, had this been caused by bug killing one might assume, once the meds were stopped and the dust had cleared, to see some improvement. In fact, many fervent MRers assured me that that was what would happen. But the improvement never came.

LymeMD suggests that Lyme patients fit Marshall's profile of low 25-D and high 1,25-D. But by my observations this is not the case. An informal poll on any Lyme board will show numbers all over the place (why not do one here?). In fact, when the MP started recruiting from CFS and Lyme communities (go back to Lymenet messages from 2004), the D results were so scattered, so different than the sarcies who had been relatively consistent, that the MP folks changed the rules and made up new jargon in order to fit this discrepancy into their theory.

Shawn said...

A new study indicates that bacteria boost NOS to counter antibiotics.

"They found the enzymes responsible for producing nitric oxide were activated specifically in response to the presence of the antibiotics."

"The researchers then showed that eliminating nitric oxide production in the bacteria allowed the antibiotics to work at lower, less toxic doses."

I have found material that supports the idea that Vitamin D increases NOS.

Dr. Paul Cheney says that most CFS patients he's seen have had upregulated NO.

What if.... The Marshall people, by restricting Vitamin D, were unknowingly lowering NO all along?