Vitamins and Supplements

I have indicated in the past that I try to approach Lyme and associated infections from a conservative "allopathic" perspective. I am skeptical of supplements. I have treated many hundreds of patients and had much success without using supplements. So when I read: "Most LLMDs follow Dr. Burrascano's recommendations," because he is the "Man," I feel compelled to respond. My comments here should not be considered an attempt to disparage Dr. Burrascano or his beliefs. Rather, I am simply putting forth an alternative point of view.

I am concerned when the section on supplements recommends that patients buy a pill organizer just for Lyme related supplements. The implication that our bodies cannot heal without a plethora of artificial supplements runs counter to my clinical instincts. I believe that the body, given a reasonably balanced diet, is normally able to extract all the micro-nutrients it requires. Let me explain the distinction between micro-nutrients and macro-nutrients. Micro-nutrients, like vitamins, are molecules our body requires in trace amounts. They are co-factors, required by enzymes, which promote critical metabolic processes in our bodies. Macro-nutrients, on the other hand, are the major fuels and building blocks that our bodies require, including carbohydrates, proteins and fats. Plant derived vitamins are also called phytochemicals. It has been found that vitamins do not act alone. Our bodies have evolved so that a symphony of phytochemicals act in concert, to promote the metabolic processes required in our bodies. Several well documented studies with individual vitamins, such as vitamin C, vitamin E and beta-carotene have shown unexpected negative results, rather than beneficial ones. For example, for decades cardiologists promoted vitamin E as an anti-oxidant which was expected to block the deposit of oxidized cholesterol in arteries. When the study was done, no benefits were seen. Cardiologists no longer recommend this supplement. Two theories have been proposed for these findings: 1)Isolated vitamins, ingested outside the panoply of associated phytochemicals, are ineffective or harmful and 2) artificial vitamins do not act in the same way as natural, food derived vitamins.

Dr. Burrascano introduces the section on recommended vitamins and supplements by indicating that the benefits of some of the vitamins/supplements has been verified by controlled evidence based studies. What studies- which vitamins? If such data exists, its basis should be put forth, allowing readers the opportunity to make their own critical appraisals. The author's conclusions cannot be accepted blindly, especially when the issues are controversial, not to mention potentially very expensive. (I have not foot noted my references- but I am not making firm recommendations- I am only sharing my opinions). The reader should keep in mind that it is not necessary to prove a negative assertion, only a positive one.

Dr. Burrascano puts his reputation on a limb when the supplements are not suggested but rather "required."

Probiotics: Most physicians treating Lyme disease with long term antibiotics would strongly recommend these supplements. Many of us would not recommend specific brands. Many practicing physicians, including myself, would recommend that a brand of Sacchromyces be included, since this yeast based probiotic is not killed by the antibiotics.

Multivitamin: There is no evidence that this is helpful. I do not recommend it, neither do I discourage it.

Co-enzyme Q10: I do not routinely recommend this. It has been shown to be helpful for patients with disease of the heart muscle. It does help the mitochondria increase energy output in some cases. If there is a human study regarding this supplement and its benefits in cardiac Lyme, as suggested, then this information should be brought out. Q10 has been shown to be useful for diseased heart muscle from other medical illnesses. This does not prove that it is beneficial when the heart muscle is not diseased. For example, vitamin C is an essential supplement if someone has a deficiency disease called scurvy. This does not prove that a person without scurvy will accrue any benefits from taking extra vitamin C. Some patients feel that Q10 gives them extra energy. I do not discourage patients from experimenting with this on a case by case basis. It is not required.
My research shows that there is no basis for restricting the supplement while taking Mepron or Malarone.

Alpha Lippoic acid: I don't recommend. What evidence?

B vitamins: I only recommend if there is evidence of deficiency. Again, what are the clinical studies referred to.

Magnesium: It is documented to help with muscle cramps. It is depleted by diuretics.
In general I dot recommend it. There is no evidence to support its use.

Essential fatty acids: I recommend a diet high in fish, whole grains, nuts and seeds. If a proper diet cannot be followed there may be a scientific basis for these supplements. I do not consider their use routine or mandatory.

NT factor, Carnitine, SAM-e: No evidence- not recommended. SAM-e may help with depression. In Lyme patients depression may be modulated by poor frontal lobe function (SPECT scans), sensitivity to glutamine, fatigue and other specific neuro-chemical dysfunctions. Specific drugs may be recommended based on these known or suspected abnormalities.

Green tea? What is the evidence? The "hot topic" is coffee. It is reported to have beneficial effects in the brain and liver. There is some scientific evidence to promote these claims. This issue is of interest. It is not recommended or required.

Cordy Max and other herbal therapies: I confess complete ignorance- but I have helped patients without such things. Herbalists are specialists who have spent many years perfecting their art. I don't think that allopathic doctors should not casually recommend such things based on the unsupported recommendations of one practitioner. Patients who wish to pursue such alternative options should consult with a practitioner fully conversant with this discipline.

Glucosamine: Yes. It has been shown to work as an anti-inflammatory and reduce joint pain. In my experience, pharmaceutical anti-inflammatory medicines like Celebrex are much more effective. Other natural anti-inflammatories, such as Limbrel and Wobenzym may also have benefits. These supplements are only helpful for controlling symptoms.

Vitamin C: No. No evidence that it helps. It has been suggested by some (Donta) that it might interfere with Plaquenil, if this drug is being used.

Creatine: This is another mitochondria energy component. It may be helpful if weakness or muscle dysfunction is present. The comment about its benefits in ALS patients is evidence based. There is no evidence to support its routine use.

Milk thistle: I don't recommend. It has been thought by some to have beneficial effects in the liver. Coffee may work better.

Methyl B12: Very expensive. If vitamin B12 deficiency is present there are much more cost effective supplements. I do not use or recommend. Where is the evidence?

Vitamin D: Very controversial. I do not recommend it. Most Lyme patients, in my experience, have high levels of vitamin D dihydroxy 1,25, the active form. Vitamin D is not actually a vitamin, it is a hormone. It has active immunological effects. The issue is very complex and has been discussed elsewhere in this blog. My thoughts about it are in a state of flux. I plan on re-visiting this topic in the near future.

Let me re-iterate. I am not making this post to discredit, or belittle the recommendations of this well known pioneer in the field of Lyme medicine. I am raising questions and sharing my experiences and beliefs. I do feel that patients should be well informed about treatment options and make decisions based on knowledge rather than ignorance. Doctors are not "God." They do their best to make recommendations based on their evaluation of an unbelievably complex soup of information. I am concerned about many patients I have seen, who have left the offices of other physicians, having spent a fortune on a shopping bag full of supplements, without experiencing any clinical improvements. They have also not received the benefits of treatments which are steeped in the available scientific evidence and theory regarding this complex and frequently baffling syndrome of infection and illness.

Flagyl: On the fence

Why do you need Flagyl or Tindamax? The conventional wisdom is that treatment needs to address all three forms of the bacteria. After all, the spirochete morphs into L-forms and cyst forms; if these different morphologies are not targeted the disease cannot be "cured." Otherwise, the bacteria cannot be eradicated. The cysts after all, become be a reservoir of disease waiting for the right conditions, to become active spirochetes. The science, the bacteriology, the immunology tells us something different. The body cannot be sterilized of Lyme or Bb bacteria. The intracellular niche is too protected. The immune response to intracellular bacteria is not far reaching enough. Despite clinical remission, Bb will forever persist within our cells and tissues. Many patients who are in a clinically remission relapse significantly when "cyts busting" drugs are added. The immune system becomes activated; inflammatory cytokines are produced and the symptoms return. The patient "Herxes" all over again. Frequently cognitive dysfunction worsens, joint pain and fatigue return as well as other symptoms. And to what end?

Yes- Cystic and granular forms of Bb have been demonstrated in the brain. In some cases the addition of Flagyl can lead to cognitive improvement. I don't think this is usually the case. Many cyst and granular forms have found under biofilms. My suspicion is that biofilms are not a cause for alarm. At any rate, there is no way to reach or kill such germs. By far, the biggest source of foreign bacteria is found in our oral cavities. These bacteria contained within biofilms generally cause us no adverse health consequences. It is only when the biolfims become broken down by active infection that these previously walled of colonies of bacteria become problematic. Sometimes- anti-cyst therapy seems to improve mental clarity. If cognitive issues persist, then the drugs can be tried. The mechanism by which this occurs in unclear to me. For the most part treating Bb cysts may be a lot like swatting a stick at an otherwise quiet hornet's nest.

The goal of successful Lyme therapy is to eliminate symptoms and restore health.

These would be parasites(Lyme Bb) have the nasty habit of stimulating our immune responses in ways which are deleterious. The infection- but perhaps to a greater extent, our immune responses makes us sick. If we lower the spirochete load, minimize the ability of the germs to replicate and reduce or eliminate the harmful immune responses, then hopefully a clinical remission can be established.

In order to achieve this balance it may be necessary to keep most patients on persistent low dose antibiotic therapy. This maintains a perpetually hostile environment for cystic forms. No- Minocin for example won't kill the cysts, but if any cysts convert into spirochetes, antimicrobial will be on board and nip the conversion in the bud. Disease reactivation will not occur.

C6 peptide

I have noticed a change in C6 antibody results. They are generally much lower than they were a year ago. The test measures an ELISA reaction to ViSE, a surface protein unique to Bb. The ability of the Lyme bacteria to alter this surface antigen has been well described. It is not surprising that reactivity would be variable. I would expect this to occur in individual patients; instead the change in reactivity covers a wide swath of patients, many of whom have not been treated. On the other hand, a subset of patients who have been treated extensively with antibiotics "seroconvert" with regard to this parameter. I have noted that the test measures an IgG antibody to a synthetic version of this antigen. Perhaps the test is failing because it fails to measure IgM responses which are more prominent in Lyme patients. Typically, in the past Western Blot positive Lyme patients had C6 peptide index levels, on average of 0.2 to 0.4. Recently I have seen WB positve patients with C6 indices approaching zero.

Pneumonia, leg swelling and one sided paralysis

Two years ago a 32 year old female was admitted to the hospital for atypical pneumonia- pulmonary infiltrates and a high fever. Her illness was preceded by a rash on her legs, fever, cough and severe diffuse joint pains. In the hospital she was treated with two weeks of IV Rocephin and Zithromax, to "cover" her for various causes of pneumonia. When I saw her in the office for a follow up visit I noted a significant circular red rash on both lower limbs. Labs at that time showed an elevated CRP of 12, a borderline ANA antibody and a single 41 IgG WB Lyme band out of the standard 13 bands. I continued oral antibiotics. The rash improved within a couple of weeks. She complained only of fatigue and nausea. The physicians who saw her initially could not explain her findings. It was suggested that she had an autoimmune disease. The rash was biopsied. The findings were: non-specific lymphocytic dermatitis. She continued antibiotics for several months and generally did well. Additional symptoms included: persistent fatigue, strange visual changes and bouts of numbness and tingling. She developed right upper quadrant abdominal pain, suggesting gall bladder disease; this improved without intervention. After 6 months of antibiotics, she stopped them without consulting with me. I saw her about 2 months later. She had been hospitalized again. She had experienced acute weakness of her extremities and a loss of sensation in both legs. She also experienced transient double vision. The neurologists who evaluated her listed various differential causes: MS, stroke, Guillain-Barre syndrome and vasculitis. Her work up was negative. She was sent home without a diagnosis. In the medical history provided by the neurologist,"Lyme disease" was mentioned parenthetically. The verbiage in the consultation notes essentially mocked the diagnosis, treatment and physician.

Repeat lab testing showed that a C6 peptide antibody test sero-converted from 0.29 to 1.2. This information was not considered relevant.

The patient improved and her symptoms were stable when she came to see me after this adventure in the local hospital.

I explained to the patient that I felt her symptoms and findings were consistent with chronic Lyme infection. My exam revealed numerous neurological abnormalities- not noted by the neurologists. I don't think she fully believed me. She works in a doctor's office and was hearing many conflicting points of view. Despite this, she continued antibiotics for an additional 4 months.

Two months after stopping antibiotics (again!) she came into my office. She had marked numbness and weakness of the left side, upper and lower extremity. She had nearly absent pinprick and vibratory sensations of both legs. This time she was really sick. Her presentation was typical of MS or an acute stroke. I thought it was all Lyme related. She decided to follow my recommendations. An MRI of brain and spine were normal. She was immediately started on IV Rocephin along with a short course of IV steroids.

She experienced a brief episode of confusion. Within 4 days the weakness was improving. Withing a month she was 80% better. Within 8 weeks she was almost normal.

She has stayed on antibiotics and done well since this episode. She continues to have only minor symptoms. Her markers of inflammation have improved. Her CRP is less than one. Her ANA is negative. She continues to have abnormal physical findings which are slowly improving. Needless to say, she is no longer anxious to stop antibiotics. I think she agrees with my approach and has become a reader of this blog.

She came to me by accident. I was/am her primary care physician. I can imagine how things might have turned out if she had been treated by standard paradigms. Her primary care physician would have said: "I don't know what it is." A rheumatologist would have diagnosed a non-specific autoimmune disorder and treated her with immune modulating therapy. A neurologist would have diagnosed an atypical form of MS and suggested other therapy. She might be disabled with paralysis on one side of her body. She would likely suffer with profound cognitive deficits and diffuse pains.
Perhaps fibromyalgia would be added to the list of symptoms. It seems unlikely that she would be working full time and taking care of her young child. But she is.

These other physicians who encountered my patient on this journey are unaware of her story. She was a consult, an undiagnosed case- lost to follow up. They are busy- seeing new patients and are not looking back.

Valcyte

Patients suffering with "chronic fatigue syndrome," evidence of immune dysfunction- alterations in CD8/CD4 cells and elevated antibodies to a variety of viruses have shown marked improvement in symptoms after taking the anti-viral drug, Valcyte. Valcyte is only FDA approved for CMV retinitis seen in HIV patients; but it is active against other viruses as well. The recommended course of therapy is six months. The best evidence comes from a pilot study from Stanford University. The symptoms of fatigue and cognitive dysfunction closely parallel those seen in my "chronic Lyme" patients. Specifically, patients with evidence of EBV and HHV6/7 have been studied. Other reports include CMV virus, another potential cause of chronic fatigue, in the subset of responders.

Lyme patients have immune dysregulation. High titers of antibodies directed at these viruses are routinely seen. My working hypothesis has been that Lyme- the gatekeeper germ suppresses the immune system which allows these chronic, generally contained, viruses to flourish. Perhaps a sort of vicious cycle betters describes the process. As the viruses replicate, a increasing burden to the immune system makes elimination of Lyme and other opportunistic pathogens more difficult. The various germs in a sense, conspire to weaken one's defenses to all the problematic germs. Lyme treatment failures may occur because the immune defenses never heal adequately to a level which allows control of Lyme. The same arguments have been marshaled regarding other typical, Lyme associated, co-infections.

This drug is toxic to the bone marrow and requires close supervision. The study at Standford is now providing an evidence based justification for trying this drug.
Of course it is used widely in California where medical boards are prohibited from censuring physicians who treat diseases based on alternate hypotheses. Not here.

The early evidence is favorable.

The paradigm, as always, is in a constant state of flux.

CD57

What do these letters and numbers mean? The study of immunology is complex and confusing. I will try to simplify this, but it still may be hard to follow. Don't worry- most doctors don't get it either. Lymphocytes are the major white blood cells involved in the body's immune responses to infection- and other conditions, including cancer. They have been subdivided based on receptors located on their surface. The "expression" of these receptors is the basis for categorizing the various types of lymphocytes. The various types of lymphocytes have been shown to have specific functions. Lymphocytes express multiple receptors. The CD8 cells are generally referred to as killer T cells, not to be confused with natural killer T cells. The CD4 cells are referred to as helper T cells.

The initial response, the innate response, is directed by lymphocytes. The natural killer T cells, defined by receptors found on their surface, constitute a very tiny percentage of the T cell population. Nonetheless, they have an important role in fighting infection. Laboratory scientists have developed specialized technology which allows for the separation of these various subsets of lymphocytes.(Flow cytometry).

Most natural killer T cells (NKT cells) are associated with a surface receptor referred to as CD56. The CD57 marker is associated with a smaller subset of NKT cells. Interestingly, these surface receptors (CD57) have been found on both CD8 cells and CD4 cells. Normally, one would expect these markers to be found on CD8 cells- the population of killer T cells.

A powerful CD57 response is associated with Lyme infection and with other bacteria as well. Other spirochetes do not invoke this response because the structure of their cell wall is different. The unique thing about Lyme (Bb) is that it has lipo-polysacharides on its cell wall. This is antigenic(antibody producing) material, which is devoid of protein. CD57 cells respond to this type of antigen whereas other NKT cells do not.

The initial immune reaction- the innate response, involves the mobilization of CD57 cells and other T cells as well as cytokines and other chemicals. Normally, a secondary acquired immune response should follow the innate response. This is mediated by B cells aided by helper T cells. Ultimately, the acquired immune response fails. Lyme (Bb) is driven inside the cells as L-forms. B cell responses do not work here. It then falls on T cell responses to become the body's major immune response needed to keep Lyme and other intracellular germs at bay.

CD57 responses involve the same pro-inflammatory cytokines as seen in Th1 helper T cell responses.

If CD57 responses are low, it may mean that these cells are being consumed by the immune system in the fight against Lyme. If they are high, it may mean that the body is busy cranking out the T cells to assist in the fight against Lyme.

There is little published regarding the clinical usefulness of this test. Dr. Stricker has reported that this measurement "May" be helpful in assessing the degree of illness seen in chronic Lyme patients.

So I have been ordering this test for years. Thousands. Unfortunately, I am left with the conclusion that it has been of very little help to my patients. I have seen no correlation between CD57 and disease activity. Patients in clinical remission may have very low levels and patients with end stage tertiary Lyme disease may have very high levels. Individual immune responses are difficult to predict. Dr. Burrascano has suggested that the CD57 test might be an inexpensive way to screen for Lyme disease. I do not agree. Physicians may order CD57 levels because they are looking for evidence to support the diagnosis. I do not think this approach will not hold up to careful scrutiny. Many patients unfortunately are getting the awful 13 band test performed at "mill labs." Patients don't want to spend the money to get a decent Lyme test. I do throw out a wide net looking for a variety of markers associated with Lyme disease. I could argue that the vitamin D reversal pattern, a possible marker of the Th1 response, is a much better screen for patients with Lyme disease and other chronic intracellular infections.

I have seen recent published statements claiming that it is not known how CD57 and Lyme are associated. My research shows otherwise. (If you could follow any of what I said about it). However, in my opinion and experience, this marker has not been clinically useful.

What I believe: 2009- A brief overview

We are no closer to any acceptance by the medical community of the existence of chronic Lyme disease. Patients and their physicians alike are dismissed.

Lyme is difficult to treat. IV antibiotics are frequently required. In my experience, the disease is frequently under-treated. Excessive concerns about severe Herxheimer reactions are frequently associated with inadequate therapy.

The goal of therapy is clinical remission. The persistence of the organism in cells makes it virtually impossible to eradicate. Despite this, some patients may experience a sustained remission off antibiotics. Other patients may have a remission maintained with low doses of antibiotics.

We still know very little about the disease. I would be concerned about claims that a physician is a "Lyme expert." No such experts exist at this time. The term LLMD has no specific meaning.

Patients frequently harbor a parasite that may or may not be a species of Babesia. The existence of this parasite may be impossible to prove based on current diagnostic standards. Treatment of this entity is critical for recovery of many- not all patients.

Ehrlichia is a fairly common co-infection. It resides in white blood cells. It too can be somewhat difficult to treat, but it usually responds to antibiotics well.

Bartonella appears to be a rare coinfection based on objective measurements. The optimal treatment for this bacteria is a matter of debate.

Bartonella like organism- "BLO" does not exist.(My opinion)

There are major, yet unidentified, co-infections- at least one of which is very difficult to treat. This is the small, highly motile, gram negative bacteria seen in the blood of most Lyme patients. This bacteria is highly resistant to most antibiotics. At this time it is not clear how to treat it. An unidentified small protozoan has also been seen in the blood of Lyme patients. This too is unidentified, but may account for some the clinical responses seen with Flagyl and anti-malaria drugs.

Rickettsia species may be frequently transmitted as a co-infection, but are probably eliminated with anti-Lyme therapy. Atypical Rickettsia have been identified in 20% of Ixodes ticks.

Mycoplasma species and Chlamydia pneumonia are frequently present in Lyme patients. They are intracellular and are also difficult to eliminate. Their role in the pathogenesis of the syndrome is not well known.

Standard allopathic treatments are very effective. I believe the role of CAM in managing this disease has been over emphasized in most quarters.

Therapy must be individualized. It remains difficult to predict how individual patients will respond to any given regimen.

Chronic Lyme disease is associated with objective measurements and findings.

The role of vitamin D remains unanswered. For now, I see it as a marker which relates to an immunological response to infection.

CD57 counts appear to be of little clinical benefit.

Many, if not most of the symptoms associated with chronic Lyme disease, reflect the bodies immunological reactions to infection, rather than infection per say. Auto-immune responses play a large role in the pathogenesis of the disease syndrome.

Proven antibiotics (classes) include: beta-lactams. macrolides, quinolones, rifampin, Flagyl/Tindamax, anti-malarials- Plaquenil, Malarone, Mepron, clindamycin- related to macrolides, tetracycalines and artemesin. I see no significant role for sulfa drugs like Bactrim.

Complementary medicines which appear helpful include: Bile binders- Welchol and Questran. I remain unconvinced about any others. I am cautious about recommending things which have no proven clinical benefits.

Information about Lyme and tick borne illness remains very confusing and contradictory. Lyme patients need to become well informed about their illness so that they can partner with their physician. Patients must also be informed so that can decide whether or not a physician's approach makes sense to them.

Patients and doctors should not be wed to a particular paradigm. If a therapy isn't working then something else should be tried.

I do not believe it is ethical for physicians to sell supplements and books to patients from there office. It may be legal, but I see it as a conflict of interest.

The vast majority, yes 90% or more of patients, experience significant improvement when the correct therapy has been established. There remains a small minority of patients who are resistant to treatment. Even these patients generally improve to a variable extent, if the physician is both creative and persistent.

Multi-specialty Lyme clinics must be developed in the coming years.