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Lead and Homocysteine Levels in a Series of Individuals Diagnosed with Parkinson’s Disease

Dr. Kara Fitzgerald

I recently saw a patient who had been diagnosed with idiopathic Parkinson’s disease (PD) in 2000 when she was just 39 years old.  Her history was compelling in that everyone in her family was well --no neurological diseases, parents hearty and healthy at 80 -- and she herself was a healthy child. However, she has a daughter with autism.

It turns out this woman and her husband renovated a lead-saturated 100-year-old Chicago house over the course of 10 years -- in the 1990s. She gave birth to her daughter-who was later diagnosed with the neurological condition autism--while in the house in 1998, around the time she first noticed a tremor.

Dr Kara Fitzgerald ND

When urine toxic metals were recently assessed in this patient, her lead (Pb) level was extremely high. In fact, it was eleven times the cut-off limit (her result was 22ug/24 hours; the cut-off limit is 2ug/24h hours). This finding suggests that she has a significant, long-time body burden of lead.

Yes, lead toxicity is a contributing cause of PD and has been implicated in autism.

In PD, lead has been shown to directly damage dopaminergic neurons and contribute to CNS oxidative stress. (In autism, the issue seems to be, in addition to CNS oxidative damage, compromised removal (biotransformation) of lead due to lesions in glutathione conjugation and methylation- more on that below.)

There are currently about one million individuals diagnosed with PD in the US; as with most neurological diseases, its numbers are rising rather rapidly. Diagnosis is made only after the disease shows up clinically— that is, after 60-80% of dopaminergic neurons in the substantia nigra are lost. There are no great biomarkers to conclusively identify disease before this late stage, BUT, if we think about it from a functional/systems medicine perspective, early clues abound.

There is no smoking gun genetic mutation in PD. Yes, there are some genetic mutations that increase risk, (here’s a recent free full text published by PLOS genetics and written by 23 & Me), but having a PD-associated mutation and developing PD isn’t a slam dunk. It’s now well accepted that Parkinson’s Disease, like most complex, chronic conditions is largely caused by chronic environmental exposures, including pesticides, herbicides, toxic metals and the like.

Understanding the toxic connection, it becomes urgent that we regularly evaluate toxin exposures in our patients by taking a careful environmental exposure history and using appropriate labs- such as urine and/or blood toxic metals. When we find concerns, we need to address them immediately by removing the exposure sources and treating the patient, ideally BEFORE they develop clinically apparent complications such as PD.

Data mining in Parkinson’s disease

When I was completing postdoctoral training at a clinical laboratory, we conducted an informal “data mining” project, looking at nutrient imbalances and the presence of toxins in individuals diagnosed with Parkinson’s disease. I was struck by consistent patterns of imbalances. For instance, of the 32 individuals diagnosed with PD who had metals tested, over 60% had higher-than-average to very high lead levels. Additionally, 12 people had higher mercury and 11 had higher aluminum levels.  

Of the 10 individuals with PD who had homocysteine levels assessed, all were on the higher side, ranging from 8.7 to 22.6.  Six of the 10 individuals with PD had frankly elevated homocysteine. By comparison, a control group of six adults not diagnosed with PD, the homocysteine range was a much lower 5.4 to 9.3.

Incidentally, the highest homocysteine level (22.4) was in the same individual who had the highest lead level.


Methylation and sulfuration: I know you know it by heart…

 

There are a few ways to think about these data

  • Homocysteine is a marker of methylation activity. When it’s high (or low- as can be seen in autism), methylation is compromised. Methylation is involved in-among other myriad things- removing toxic metals from the body.
  •  Methylation and sulfuration (think glutathione production) are very interrelated- see how homocysteine is the link between the two pathways in the figure above I borrowed from the net.
  • When methylation is inhibited--suggested by a HIGH or LOW homocysteine-- sulfuration is compromised, too. This means a multitude of toxins aren’t being removed sufficiently AND antioxidant capability in the body is compromised. Double whammy
  • No surprise: elevated homocysteine is seen in lead toxicity. Somewhat surprising: L-Dopa- the main therapy in PD-- also results in homocysteine elevation. This is because COMT, the enzyme that metabolizes L-dopa, requires the methyl donor cofactor s-adenosylmethionine (see the figure above). L-dopa therapy depletes methylation causing a spike in homocysteine. We can infer that L-dopa therapy may hinder removal of the very toxins that contributed to the PD in the first place.


BUT….We certainly cannot take PD patients off L-dopa. It’s a critical treatment given the damaged dopaminergic neurons.

Our focus must be around carefully supporting normal methylation/sulfuration in this population. Anyone practicing functional medicine knows the drill: folate, B12, betaine and glutathione or the glutathione precursor n-acetylcysteine.  

Watch a video of Dr. Perlmutter using IV glutathione in a PD patient.

The dance for us as clinicians in treating the individual with PD is to normalize/assist in the removal of toxins by addressing methylation and sulfuration, but not boost methylation so aggressively that we promote excess metabolism of L-dopa.  (When PD patients are given the COMT cofactor s-adenosylmethionine, it worsens symptoms.) It is therefore imperative that we monitor homocysteine, toxin levels and clinical symptoms when implementing this approach. Make sense?

Understand that while addressing methylation/sulfuration in the PD population is an essential component to a functional/systems approach, it’s only one area in a much larger systems approach. And as with autism, the earlier we start, the better the outcome. Ideally, we’re preventing the disease by getting there before it starts…….

A little more on lead…

Living in an old house is the most common cause of lead exposure in the US. And it’s not just renovating an old house. Just generating airborne lead-ladened paint particles from opening and closing windows is a huge exposure source, and inhalation is the most efficient route of lead absorption. But GI absorption is significant as well. Crops grown in lead-exposed soil (think soil saturated with leaded gas) bioaccumulate the toxin. We can use the bioaccumulation phenomenon to remediate soil, but just don’t eat those plants!

We can also find lead in common household items- such as the ceramics we eat on- especially those made in China. I recommend patients purchase at-home lead test kits for testing. I like 3M Lead Check sticks. Get them at Amazon.


A patient recently emailed this: A positive finding for lead on a ceramic dinner plate.


Blood lead cut-off levels have been lowered and lowered over time. This is a figure borrowed from the CDC. See Lead, No Safe Exposure Levels.   

BRCA Mutations, Breast Cancer and Epigenetics: Is the Risk Modifiable?

Dr. Kara Fitzgerald

It’s been a busy, productive and rather amazing Fall. Lots to write about. In celebration of the gorgeous New England weather, I’ve been spending much time on my bike the last couple of months, and it feels great!

Riding on Ridgefield back roads. Nothing beats it.

I just returned from speaking at the Nutri Advanced conference in London where Drs. Jeff Bland, Andrea Girman and Joe Pizzorno also presented.  It was a great conference—the largest yet. UK is embracing Functional Medicine. And London was also absolutely lovely the week I was there.

The Millennium bridge, crossing the Thames from St. Paul’s to the Tate Modern. With Dr. Andrea Girman. We just saw the play Light Princess- words and music by Tori Amos. Amazing!

As always, I was thrilled to hear Dr. Bland speak.  A founding father of Functional Medicine (he coined the term), his words nourish intellectually and also spiritually. Listening to him feels like receiving transmission from a Zen master who happens to have a PhD in nutritional biochemistry.

Jeff presented on epigenetics, that is, the way in which environment can shape our DNA expression and determine whether or not we get a particular disease.

So, just because you have the DNA associated with a particular disease doesn’t mean you’re getting the disease. This is such an empowering statement. I’ll say it again: Just because you have the DNA, doesn’t mean you’re getting the disease.

Jeff provided a potent example of this truth: The BRCA1 and BRCA2 mutations are very closely associated with breast and ovarian cancer. Indeed, if you have a BRCA mutation, your lifetime risk of developing breast cancer is greater than 80%. Recall that Angelina Jolie—who has the BRCA1 mutation--just had a double mastectomy to significantly reduce her risk of developing breast cancer.

If you have a BRCA mutation, it seems that you’re going to get cancer, regardless of your health choices, doesn’t it? I certainly admire Angelina’s courage to reduce her risk.

However, if we look into the history of the BRCA mutations and cancer risk, we find that before 1940, the risk was 24% with the BRCA mutation, not 82%, as it is today. Clearly, environment is playing a big role in the development of breast cancer even with the BRCA mutations.

What’s going on?

Dr. Mary King, the scientist who discovered the BRCA mutations, recognized the environmental influence on cancer risk. She specifically cited adolescent obesity, lack of exercise and early age of menarche as factors in the rise of BRCA-associated cancers. 

I began thinking about the BRCA mutations and environmental influence in 2007 when I was working at Metametrix Laboratory. My attention was on the influence of fatty acids on hormone-sensitive cancers. A big question for me was: What does a functioning BRCA protein do in the body? As I was drilling down into the literature, I made a fascinating discovery that I rarely see discussed. This discovery gave me a clear treatment direction on how we might reduce risk for individuals with the BRCA mutation.

What does a normally functioning BRCA protein do in the body?

Functioning BRCA proteins are huge, complex structures involved in a good deal of regulatory activity in the body. They are recognized as tumor suppressor genes; they repair DNA.

A lesser recognized BRCA1 role has to do with its ability to potently down-regulate (inhibit) the body’s production of the enzyme aromatase.

What does aromatase do in the body, and why do we want to inhibit it?

Aromatase is the enzyme involved in making estrogen. And in this particular context, estrogen promotes cancers like breast and ovarian. You’ve likely heard of aromatase inhibitors -- drugs that are commonly used to treat these cancers. (Note that estrogen has many essential, healthy, anti-inflammatory roles as well; but that’s for another discussion.)

Not surprisingly, if you look at aromatase in those with the BRCA1 mutation, it’s a lot higher than it should be. So there’s a lot more estrogen than there should be -- hence the cancer risk.

Back to the fatty acid story.

When I discovered the BRCA1/aromatase link, I also learned that the pro-inflammatory fatty acid, called arachidonic acid, makes a compound called PGE2.  PGE2 inhibits the good deeds of a normal BRCA1 and promotes aggressive aromatase expression. This results in lots of estrogen production and increased breast and ovarian cancer risk.

In other words, PGE2, from arachidonic acid, can behave like a BRCA1 mutation.

Arachidonic acid (AA) is an omega 6 fatty acid. Some AA is essential for a normal immune response; but anyone eating a typical diabetogenic diet — nutrient-void, too much sugar, simple carb and inflammatory omega 6 fats -- is making way too much arachidonic acid (and therefore PGE2). Globally — not just in the West -- most of us eat this unhealthy diet.

Therefore, one of the most fundamental ways we combat breast and ovarian cancer is by eating a healthy, anti-inflammatory diet. Those with the BRCA mutation? All the more necessary, even urgent, is the anti-inflammatory diet.

Returning to Dr. King’s observations, everything that she suggests will reduce excess or toxic estrogen exposures: More exercise, less obesity (starting early), better diets, later menarche. And of course, all of these are known to reduce cancer risk. (Early menarche is influenced by early estrogen exposures. Therefore, if you want to influence your daughter’s menarche, these changes should be made even before you conceive her, but certainly in early childhood.)

I want this blog to feel empowering for those with the BRCA mutations, or those concerned about hormone-sensitive cancers. The reality is there is much we can do to minimize the impact of estrogens on the body. Any good integrative doctor can come up with a robust to-do list. The fact is, many, many botanicals can interfere with the production of PGE2. If we pack our body full of the good omega 3 fatty acids, also, we will inhibit PGE2 availability. And as I mentioned, perhaps the most powerful factor is an anti-inflammatory eating plan.

Here are just a few of my anti-inflammatory/estrogen modulating/cancer-protective favorites:

  • High dose omega 3 fatty acids
  • Curcumin
  • Garlic
  • Ginger
  • Reduce stress (stress > inflammation > PGE2 > aromatase > estrogen)
  • Resolve insulin resistance (high insulin increases arachidonic acid, which will ultimately increase estrogen)
  • Avoid toxins such as BPA, pesticides, herbicides, parabens, phthalates, etc. All have an estrogenic effect and will contribute to the estrogen pool.
  • Eat organic or clean as much as possible


What are yours?

Gluten Free and Thyroid Disease Free: An Update on Lilly

Dr. Kara Fitzgerald

Gluten Free and Thyroid Disease Free: An Update on Lilly

The last time we met, Dear Reader, before I high-tailed it on out of the blogosphere for the summer, I introduced you to Lilly and her thyroid woes. Below are her original thyroid studies that she obtained from her primary care doctor and brought to our first meeting. Lilly did not want her endgame to be levothyroxine for life. She sought a second opinion.

June, 2013. Lilly’s baseline thyroid laboratory results demonstrated autoimmune hypothyroidism (also called Hashimoto thyroiditis).

What do these results mean?

As I said in my original post, Lilly’s elevated TSH (thyroid stimulating hormone) demonstrated that her body was working awfully hard trying to get her thyroid to do its job. And the thyroid peroxidase antibody elevation --albeit mild—revealed that Lilly’s own immune system was attacking her thyroid gland.  Certainly these results were a big piece of the fatigue puzzle.

Why was Lilly’s immune system attacking her thyroid gland? I must admit, I was pretty certain gluten was involved. I wrote in my post:

It is well-documented that autoimmune hypothyroidism is associated with gluten intolerance. Indeed, celiac disease is associated with myriad autoimmune conditions, including type 1 diabetes, lupus, pernicious anemia, autoimmune hepatitis, Sjogren’s syndrome, Raynaud’s syndrome, myasthenia gravis, and autoimmune hypothyroidism.

Also recall, Dear Reader, that Lilly was entirely loath to remove gluten—her nightly crusty bread with olive oil-- from her diet. Lilly thought the whole gluten-free epidemic was another overhyped phase. (Who can blame her?) She said: “I was tested for celiac disease eight years ago and I am negative. I don’t have a gluten issue.”

I didn’t debate. But I knew that my laboratory investigations with her would include looking for gluten reactivity in its many forms. Here is what I found:

June, 2013. This lab result demonstrates that Lilly’s immune system was reacting to gluten. She didn’t have celiac -- those tests were negative -- but she was definitely sensitive to gluten.

So what did we do?

The lab result was enough to convince Lilly to stop gluten for a while. We negotiated an eight week trial. She understood that it was possible that gluten could be impacting her thyroid. She was 100% motivated to abstain from it entirely for the agreed upon time.

Not surprisingly, Lilly had micronutrient deficiencies as well, including B12 and magnesium.  Again, even though she didn’t have celiac disease, it looked like her body was having a hard time absorbing the nutrients it needed. While this is extremely common and well-documented in celiac, it’s less-recognized in gluten sensitivity.

Our treatment plan was straightforward: Avoid gluten, take B12 and minerals. I also ordered a thyroid-centric supplement (containing the nutrients selenium, zinc and tyrosine, designed to support thyroid function) that Lilly took for a little while but stopped when she ran out.

When I chatted with Lilly in July, she told me her gut was better. Gut? Lilly didn’t report any gut issues at our first meeting. It’s interesting how we can identify issues we have tolerated – sometimes for years --only after they’re no longer there!  She also said her energy was much, much better. We both knew she was on the right track.

In August, 2013, eight weeks after she started the supplements, Lilly had follow-up testing:


August, 2013. Just eight weeks after the start of going gluten free, Lilly’s thyroid function tests were normal. Her TSH and her antibodies were no longer elevated. Good job, Lilly -- No medication needed!

In functional medicine, we like to see TSH less than 2.00. Lilly’s is almost, but not quite, there. I suggested to Lilly that she restart the thyroid supplement I originally prescribed to see if we can get her into optimal range. I also suggested we continue with the gluten free plan, seeing that she’s doing so well.

Lilly responded immediately, agreeing to take the thyroid support, and proclaiming:

“No gluten since we started and no desire to have any ever again :-)”

Gluten-Free: Cliché or Catastrophe?

Dr. Kara Fitzgerald

Gluten Free: Cliché or Catastrophe?

June 10, 2013 - What do Al Roker, country singer Josh Turner and pregnant “celebutant” Kim Kardashian have in common? If you head over to www.glutenista.com, you will learn that they are all eating gluten free. As is Lady Gaga. She’s apparently “gluten free by choice.”


Lady Gaga: Gluten free by choice.

Wheat Belly. Grain Brain. Gluten Free For Dummies.

A search on the word “gluten” at www.amazon.com under “books” yields 5,569 hits.

A search on the word “gluten” at PubMed (US National Library of Medicine) yields 10,154 hits. (Granted, not all hits are relevant, but a cursory review of the first 20 research abstracts suggests that about 17 are related to gluten-influenced conditions. We can infer that the majority of those 10,154 hits are probably relevant to our topic.)

It was into this fever-pitched, Justin Bieber-styled cultural maelstrom that a lovely woman whom I’ll call Lilly came to see me recently. Lilly’s main complaint was fatigue. She’s bright, and a highly successful business woman in the health food industry. I’ve known her for years. She has seen trends come and go over her 20+ years in the business, from wearing EMF deflecting plastic badges to growing fungal super foods in the coat closet. It’s from this seasoned vantage point that she evaluates many of the über trends in her business.

And Lilly enjoys her crusty bread with extra virgin olive oil on most nights.

She forwarded her recent laboratory data to me prior to our visit. I popped the PDF open and saw this:

Lilly’s recent thyroid laboratory results demonstrate autoimmune hypothyroidism.

Her TSH (thyroid stimulating hormone) was working awfully hard trying to get her thyroid to do its job. And the thyroid peroxidase antibody elevation --albeit mild—revealed that her own immune system was attacking her thyroid gland.  Certainly these results were big piece of the fatigue puzzle. But the question is why?

It is well-documented that autoimmune hypothyroidism is associated with gluten intolerance. Indeed, celiac disease is associated with myriad autoimmune conditions, including type 1 diabetes, lupus, pernicious anemia, autoimmune hepatitis, Sjogren syndrome, Raynaud syndrome, myasthenia gravis, and autoimmune hypothyroidism.

I knew immediately that my laboratory investigations with her would include looking for gluten reactivity in its many forms.

When I mentioned this to her, she replied confidently, “I was tested for celiac disease eight years ago and I am negative. I don’t have a gluten issue.”

I didn’t debate. I just ordered the tests.

Who can blame Lilly’s skepticism? Any iconoclast worth his or her salt must be reaching for the Wonder Bread and Budweiser on principle alone. Gluten-free is everywhere. It’s ubiquitous. It can get obnoxious. 

But the unfortunate reality is that the incidence of adult-onset celiac disease is rising, rising, rising. In Minnesota alone, the incidence of celiac disease tripled in the last 10 years.  And the research around gluten sensitivity-- reactivity to gluten with or without accompanying celiac genetics--is also rising. 

Thus, even if Lilly tested negative eight years ago, and doesn’t have the celiac genetics-- it doesn’t mean that gluten hasn’t become a problem for her since then.

Non-celiac gluten sensitivity (GS) has been associated with neurodevelopmental and neurodegenerative conditions, including autism, dementia and ataxia. GS has also been associated with schizophrenia. Indeed, in one study, maternal consumption of gliadin (a component of gluten) and subsequent production of IgG anti-gliadin antibodies was associated with increased risk of psychosis in exposed offspring. In other words- if mom develops an immune response to gluten that results in a rise in IgG anti-gliadin antibodies while pregnant, those IgG antibodies can cross the placental barrier and potentially damage baby’s neurological development. Scary stuff.

It’s an awkward alliance that I and so many of my colleagues find ourselves in with the Kardashians, the Rokers and the Gagas of the world. Integrative physicians and practitioners are, by nature, iconoclastic.  I can assure you however, that long after the lights fade on the gluten-free fad, and the Amazon hits dwindle, the gluten-free dietary prescription will continue as it’s needed. 

 Lilly’s preliminary lab results just came in. Her IgG to gluten is elevated, and probably has something to do with her thyroid issues.

 

Book Review: Almost Finished

Dr. Kara Fitzgerald

BOOK REVIEW:
ALMOST FINISHED, by J.K. Bowen-Jones


June 10, 2013 - I want to introduce you to an exquisite book that I've been reading. It's called Almost Finished. It's a memoir by Justine Bowen-Jones. Justine lost her father to pancreatic cancer when she was six years old. Before he died, her father-- poet and English professor Jim Bowen--wrote her letters to accompany her through her life. This book contains his letters and her responses.

I was having a very "bullet point" kind of a day. You know: a million things to do, strong focus, move through the list, tick things off. All very constructive and emotionally void. I had 15 minutes before a meeting, so I grabbed Justine's book for a quick glance, as it had just arrived at my office.

I didn't anticipate the beauty of the book stopping me short. First, the feeling of cognitive dissonance: this book directly challenges in "bullet point" mind frame. It simply can’t be read from that place. The book won, and my day fell away from around me. Here are two very brief excerpts.

Sometimes Jim writes in poetry, as when he says to Justine;

It's not that I feel bad about it
in a common sort of way,

That you will grow old without me;

More that I will miss the ways
you will show me October.

Watching green leaves turn red again,
feeling the touch of the first snow falling.

Softly under the arc of the black street lamp
quietly standing outside

Your bedroom's frosted window,

Hearing you breathe in the warm room air

And at 12 years old, Justine writes back to him,

It's not that I feel bad,
in a common sort of way
that I have grown old,
without you.

More that,

I remember,
The dances in the rain,
And the training wheels
I no longer need,
As I look in the frosted window
Of an empty house,
Standing in a place where you once stood.

Almost Finished.by J.K. Bowen-Jones is available on amazon.
 

Potassium: The Little Element that Could (significantly reduce the cost of the global medical crisis)

Dr. Kara Fitzgerald

May 8, 2013 - Spring has sprung, the flowers are out, and if you’re not planning and planting your garden, stake out your local farmers’ markets. Of the myriad reasons to do so, chances are extremely high that you need some potassium. 93% of us do, according to the National Health and Nutrition Examination Survey (NHANES). No better way to get it than lots of fresh fruits and veggies. (Or avocado and coconut water -- my two favorite sources.)

For you skimmers, I’ll skip to the punchline of this ENL: If we had to pick one single, easy fix for the impending 47,000,000,000,000 US dollar global health care crisis it would be INCREASE FOOD SOURCE POTASSIUM. That’s it. We’d shave 20-30% right off the top of that debt. Done. And there would be a trickle-down effect of a healthy diet beyond that immediate savings, too. 


Potassium giveth
...


Sodium taketh away...

Tell Me More….

Most famously, potassium works with its little brother sodium in a delicate ratio, getting pumped in and out of cells. It’s a part of the behind-the-scenes battery using energy (ATP) to generate the pulse of life. Thinking, feeling, heart beating, moving, tasting, breathing and on and on. Potassium is one of the most fundamental players in the game. Any activity requires the action potential that potassium generates as it is being pumped around.

For sake of simplicity, I’ll call the sodium/potassium/ATPase pump The Battery of Life.

See the movie: How the Sodium Potassium Pump Works

Historically, potassium was so ubiquitous in the food supply, deficiency through diet was rare. In fact, look at a Daily Recommended Intake (DRI) table for minerals and you won’t see potassium listed! (You don’t see your DRI for oxygen, either.)

But humans have a way of messing with the most fundamental rules of life, don’t we?

If you’re eating processed foods with any regularity, you’re ingesting too much salt and too little potassium. You’re messing with the Battery of Life. Here’s how bad it is: In the US, according to NHANES, we’re ingesting almost 250% of the DRI of sodium (men: 280%, women: 208%) and only 7% of the recommended amount of potassium.

Way too much, way too little, and way too imbalanced.

Humans are the only mammals to negatively flip the intake of sodium and potassium.

What are the ramifications of this flip?

When we were writing the Elements chapter from Laboratory Evaluations in Integrative and Functional Medicine, we came up with a novel idea: Let’s create a table of the association between essential element deficiencies and top causes of death in the US. We found that potassium deficiency was associated with heart disease, cerebrovascular disease (stroke) and essential hypertension. (What we feel as symptoms of deficiency are vague and widespread but could include muscle cramps, fatigue, slower reflexes.) 

Potassium deficiency is associated with the top causes of death worldwide, including hypertension, stroke and heart disease.

About 25% of deaths globally are from heart disease and stroke alone, almost 14 million deaths annually. If we were potassium-replete, especially via fruits and veggies, how much could this number be reduced? How much money could be saved? I remember researching the global cost of hypertension and it alone was pegged at 10,000,000,000,000 US dollars annually. Hence my thesis from second paragraph above that potassium repletion through dietary intake could shave 20-30% off the impending 47 trillion US dollar global medical bill.

A note to a small subset of readers: Yeah, I know, correlation isn’t causation.  It seems a pretty tight relationship to me, though. Better still: If we get our potassium from foods, that shift alone will improve morbidity and mortality.

So, in summary, increase potassium-containing foods. A lot. Reduce processed foods. A lot. It’s an easy fix to a longer and healthier life and ultimately will save a lot of money.

Part Two: Assessing potassium and sodium status

This April I was honored to be invited to lecture on allergic disease at the annual Orthomolecular Conference in Toronto, Canada (photos below). As with most good conferences, there are usually a couple “practice changers”; that is, ideas so relevant that they move one beyond just intellectual stimulation and into immediate action and change. For me, one of this year’s came from a lecture delivered by Saul Pilar, MD, a clinician from Vancouver, BC.

Dr Pilar’s simple but powerful take-home message? Measure 24-hour urine sodium (Na+) and potassium (K+) levels in yourself and your patients.

Ruling out confounding factors like Na+/K+-altering diseases and medication effects, urine Na+ and K+ reflect what we eat. Your ratio should be in the vicinity of 1:4 sodium to potassium (1500mg/day Na+ and 4700mg/day K+). And if it’s not? Too many processed foods, too little whole foods. Easy measure, easy fix. (Note: Depending on the reference, there is some disagreement around optimal Na+ and K+ intake, but generally speaking, ballpark is 1:3 to 1:5.)

If you’re wincing at the idea of an onerous 24-hour urine collection, a cursory search of the literature reveals that we can probably get away with this “gold standard” measurement in a 12-hour collection. This suggests that an overnight collection is adequate, too.  And this test is routinely insurance-covered.

Generally speaking with regard to minerals, we want to see what’s going on inside the cell. This is usually accomplished by a red blood cell mineral assessment. Looking at intracellular potassium is a good thing, no doubt. However, given the gross imbalance in dietary intake in the case of sodium and potassium, the urine test is best.

Serum sodium and potassium are also routinely assessed; but these levels are so tightly regulated by the body, that you’ll rarely see a nutrient-induced abnormality. If K+ is abnormal in serum, evaluation for causes beyond the diet is essential.


91-year-old Prince Phillip is in the house!

And you can get a blurry glimpse of the proof in this photo. (Arrow provided for your viewing convenience.) Prince Phillip, Queen Elizabeth’s hubby, showed up at the Fairmont Royal York Hotel in Toronto, home of this year’s Orthomolecular Conference. Was he secretly hoping to catch some of the Conference? Maybe... he was in the room right next door!


Prince Phillip’s possee in the Royal York.

For all you Royal-ophiles, his full name is His Royal Highness The Prince Philip, Duke of Edinburgh, Earl of Merioneth and Baron Greenwich, KG (Knight of the Garter), KT (Knight of the Thistle), OM (Order of Merit), GBE (Knight Grand Cross of the Order of the British Empire), AC (Companion of the Order of Australia), QSO (Companion of The Queen’s Service Order), PC (Privy Counsellor). And we thought some integrative physicians have lengthy professional designations….

Also at the conference was Dr. Nicolas Gonzalez talking about Dr. John Beard, pictured on the screen. Dr Beard developed the trophoblastic theory of cancer and pioneered the use of pancreatic enzyme therapy. Very interesting.

Dr Lustig presented on sugar toxicity. Great lecture. See his video, “Sugar, the Bitter Truth,” on YouTube.

Nutra India Summit

by Dr. Kara Fitzgerald

April 15, 2013 - I had the privilege of presenting an overview of Functional Medicine at the 8th annual Nutra India Summit in Mumbai, India, a few weeks ago, some of which is available on YouTube.


Dr. Kara Fitzgerald attended the Nutra India Summit in March.

It was an amazing experience. I was impressed with the level of scholarship and scientific inquiry. Very compelling research was presented on oligosaccharides (prebiotics), probiotics and fermented foods. There were meetings on integrating pharma and nutra. And it all took place against this wonderful backdrop that is Ayurveda, India’s 5000 year old system of medicine.


Dr. Fitzgerald speaks at summit.

Dr. V. Prakash, chairman of Nutra Summit, reminded the audience that the safety studies of today are sorely inadequate when compared to the rules of Ayurveda, where safety and efficacy of a compound require no less than a century of proof before it may enter circulation. Seems hard to believe; but if the system itself is 5K years old, those substances both safe and efficacious will indeed reveal themselves.


Jain temple seen on Dr. Fitzgerald's visit.

Unfortunately, along with India’s meteoric economic development comes the dark shadow of rising chronic disease, which has supplanted infectious disease as the top cause of mortality in India.


Dr. Fitzgerald with panel at summit.

India has one of the highest rates of diabetes world-wide (and it cuts across economic lines). In fact, data from Mumbai showed that a full 95% of its inhabitants had a least one metabolic syndrome biomarker, and about 80% of Mumbaikars are overweight. Food is more plentiful now, especially the fast, fried, simple carbohydrate variety….


An ox pulls a cart through the local streets.

I was pleased to see the same calling towards wellness, however, in my colleagues at the Nutra Summit. Everyone,it seems, is deeply committed to shifting the medical paradigm.


Bombay University.

I will return to India in June to present a day-long Introduction to Functional Medicine: Focus on Case Studies.


Dr. Fitzgerald plans to return to India in June.

Viva la Commensal Biofilm

By Dr. Kara Fitzgerald


April 15, 2013 - Gastrointestinal biofilms are an important topic, and those comprised of pathogenic microbes are getting much well-deserved attention in the integrative medical community. However, in keeping with the sIgA topic, I want to give a shout-out to commensal biofilms, which are vital to GI health and deserve similar attention. 

Biofilms are everywhere, allowing bacteria to survive -- good or bad. They are found at the solid-liquid interface in most environments. Indeed, dental plaque is a biofilm, as is the slime on an icky bathtub. Biofilms are comprised of bacteria (and/or other microbes) and an extracellular matrix of excreted polymeric polysaccharides. 

Simply put: bugs + goo = slime (biofilm). 

Slime is nothing to joke about! Biofilms allow pathogenic organisms to be antibiotic resistant, up to 1000-fold by one estimate. But biofilms comprised of commensals can be our friends, modulating our immune response, supporting GI integrity and reducing inflammation. 

Research on commensal GI biofilm shows that E. coli , bifidobacteria and L. reuteri are apparently efficient producers, with the former mediated by sIgA and mucin. Research suggests commensal biofilms may be anti-inflammatory, modulate cytokine production and crowd out pathogenic biofilms. 

One study in rats with human-type flora showed improved bifidobacteria biofilm, mucus thickness, villous height, crypt depth, and mucin-producing goblet cell numbers when supplemented with inulin-type fructans. How cool is that? 

How can we tell if our GI commensal biofilm is healthy? 

On a stool test, I would be concerned if I didn’t see enough bifidobacteria, lactobacillus, commensal E. coli or sIgA. Glutamine, vitamin A and S. boulardii support sIgA production; whereas the inulin mentioned above, plus probiotic supplementation, will help facilitate commensal bacterial growth. Finally, treating inflammation and minimizing unwarranted antibiotic use should also benefit biofilm status. 

I think we can say that biofilms are little ecosystems unto themselves, where "the sum is greater than the parts.” And when we’re thinking about protection of our all-important GI microbiota, the commensal biofilm is once slimy surface we don’t want to slip away!

Metabolic Syndrome: The Deadly Quartet

By Dr. Kara Fitzgerald
metabolic syndrome
The four horsemen of the apocalypse, AKA the deadly quartet

February 23, 2013 - In a moment, I’m going to throw out a few rather depressing statistics about metabolic syndrome (MetS) and the state of health in the U.S. These stats need articulating. Over and over and over, until we get it.

We also need to be very clear on the driving forces behind our rapid descent into a disease culture. I’ll mention a couple in this blog. If we understand the root problems, chances are much higher we’ll be motivated and empowered to embrace solutions. (Perhaps only because we’re angered by the extent to which -- yet again -- health is a distant runner up to profit.)

But there are do-able solutions, which I’ll also mention shortly. And what’s particularly wonderful about the solutions is that they help not just you, your family, your neighbors, your community, but also the planet.

metabolic syndrome
metabolic syndrome
Doable solutions for all!
 
Once called “The Deadly Quartet,” MetS is comprised of elevated blood sugar, blood fat (triglycerides), blood pressure and weight (abdominal adiposity).  We’re not talking that elevated, though.  Take blood sugar, for instance. For a fasting blood sugar to be in the MetS range, it need only hit 100 mg/dL. But 100 mg/dL is actually considered a normal result by many laboratories! (Laboratory reference ranges are based on the population as a whole. So if everyone goes up, the reference range for normal will generally go up, too. An interested future blog: Understanding Reference Ranges.  I tussled with the reference range conundrum in the B12 blog, also.) The point is this: You won’t always see fasting blood sugar flagged “high” on your lab report to draw attention to the number. And unfortunately, a level of 100 mg/dL doesn’t alert many doctors either.

Do you know your fasting blood sugar number? To be sure, it’s not the whole story, but it’s arguably more important than the vaunted “total cholesterol” number that gets far more P.R. High blood sugar is the third leading cause of death in the world!1

Dig into the research a little bit further -- scientists in Texas looked at blood sugar and heart disease and found that levels above 86 mg/dL were associated with increased risk for heart disease. That’s quite a bit below 100.2

Note to self: A really good fasting blood sugar is around 86 mg/dL (or lower). Not a whole lot of folks actually clock in at 86.

We’re a culture whose “normal” promotes disease.

How about weight? 70% of us are overweight. Along with elevated blood sugar, it’s part of the deadly quartet. And obesity is the number one risk factor for Type II diabetes.3,4  Obesity is the first leading cause of death in the world, and hypertension is the fifth leading cause of death in the world. Along with elevated blood sugar, that means three of the deadly quartet are leading causes of death.

With these stats, we can’t possibly be surprised that the incidence of type II diabetes increased in the U.S by a whopping 83% between 1995 and 2010, can we? (At 226%, Oklahoma is the state with the dubious honor of highest increase in diabetes.)3,4

I’ll say it again: We’re a culture whose “normal” promotes disease.

While MetS is under-addressed by doctors, it’s well understood to be the “gateway disease,” leading to increased risk of type II diabetes, heart disease, kidney disease, cancers, dementia, autoimmune disease.  Pretty much every chronic disease to confront us is promoted by the inflammation-driven effects of MetS. A look at top causes of death in the U.S. -- most of them can be traced to the Deadly Quartet. Here’s the Center for Disease Control’s 2010 list.

Number of deaths for leading causes of death
1              *Heart disease: 597,689
2              *Cancer: 574,743
3              *Chronic lower respiratory diseases: 138,080
4              *Stroke (cerebrovascular diseases): 129,476
5              Accidents (unintentional injuries): 120,859
6              *Alzheimer's disease: 83,494
7              *Diabetes: 69,071
8              *Nephritis, nephrotic syndrome, and nephrosis: 50,476
9              *Influenza and Pneumonia: 50,097
10            Intentional self-harm (suicide): 38,364  
* Diseases directly or indirectly influenced by MetS. Even suicide, which is often associated with depression, could be driven by MetS via inflammation.5

A couple of driving forces behind our descent into a disease-centered culture.

Junk food.  Michael Moss’s brilliant article from Sunday’s New York Times Magazine, called: “The Extraordinary Science of Addictive Junk Food” says it better and with greater depth than anything I could say.

“The public and the food companies have known for decades now — or at the very least since this meeting — that sugary, salty, fatty foods are not good for us in the quantities that we consume them. So why are the diabetes and obesity and hypertension numbers still spiraling out of control? It’s not just a matter of poor willpower on the part of the consumer and a give-the-people-what-they-want attitude on the part of the food manufacturers. What I found, over four years of research and reporting, was a conscious effort — taking place in labs and marketing meetings and grocery-store aisles — to get people hooked on foods that are convenient and inexpensive.”

metabolic syndrom
Pesticides.  Other potent and often overlooked drivers of MetS and obesity are the pesticides on our foods.  

A little-acknowledged study by Lee that was released in 2006 (using National Institute of Health data) noted that exposure to six pesticides (called POPs -- persistent organic pollutants) resulted in up to a 38-fold risk for developing type II diabetes in certain individuals!6 (Where’s the publicity on this study?)  By comparison, a study looking at women smokers with a 40-year history found “a mere” 27-fold increased risk for developing lung cancer.7

Obese people were particularly vulnerable to the effects of POPs. POPs are known to accumulate in adipose and cause massive, metabolic disruption.
It’s not just about eating JUNK. It’s the TOXIC JUNK that’s particularly horrific.
 
The do-able solutions? Here’s a few. Pick a couple:

●     Plant a garden and don’t use pesticides. (even a little garden pot on the porch with a few basils and tomatoes- you’ll love it!)
●     Buy local food. Where is your farmers market?
●     Exercise. (My goal: Commuting by bike to work 3 days a week).
●     Stop most sugar, and especially the processed stuff
●     Buy food from the perimeter of the grocery store- fresh veggies and fruits; lean, clean proteins
●     Don’t buy food with chemical names in the ingredient list
●     Eat more greens, beans, lean poultry.
●     Read Mark Hyman’s “Blood Sugar Solution.”
 
When I was in medical school, a professor told us that sugar was a drug, and should be regulated as such. Her statement was an awakening for me. It was a radical idea at the time, but the time has come, hasn’t it?    
 
1.            Gray LJ, Khunti K, Williams S, et al. Let's prevent diabetes: study protocol for a cluster randomised controlled trial of an educational intervention in a multi-ethnic UK population with screen detected impaired glucose regulation. Cardiovasc Diabetol. 2012;11:56.
2.            Hoogwerf BJ, Sprecher DL, Pearce GL, et al. Blood glucose concentrations < or = 125 mg/dl and coronary heart disease risk. Am J Cardiol. Mar 1 2002;89(5):596-599.
3.            Centers for Disease Control and Prevention.  Atlanta GUSDoHaHS, Centers for Disease Control and Prevention, 2011. National diabetes fact sheet: national estimates and general information on diabetes and prediabetes in the United States, 2011. 2011.
4.            MMWR. Increasing Prevalence of Diagnosed Diabetes - United States and Puerto Rico, 1995-2010. November 16, 2012 / 61(45);918-921.
5.            Silic A, Karlovic D, Serretti A. Increased inflammation and lower platelet 5-HT in depression with metabolic syndrome. J Affect Disord. Dec 1 2012;141(1):72-78.
6.            Lee DH, Lee IK, Song K, et al. A strong dose-response relation between serum concentrations of persistent organic pollutants and diabetes: results from the National Health and Examination Survey 1999-2002. Diabetes Care. Jul 2006;29(7):1638-1644.
7.            Kligerman S, White C. Epidemiology of lung cancer in women: risk factors, survival, and screening. AJR Am J Roentgenol. Feb 2011;196(2):287-295.
 

 
Photo credits: flickr.com

 

OMG, I have the flu!!

By Dr. Kara Fitzgerald

man sniffling

I had the flu last week. Here’s the e-lament I managed to tap out on my phone in a shameless plea for sympathy:
 
“I am so sick it hurts to pee or breathe or think or move my eyes. Whaaaaa whaaaaa whaaaaaa!”
 
The sage advice I received from my BFF in response?  Swing a chicken over your head. 
 
I decided against taking her suggestion; I was too achy to swing a chicken over my head. But the worst of the flu moved through in about five days. Yes, I’m still blowing my nose and I’m tired but otherwise okay. 
 
And no, I didn’t get vaccinated. I’ve never gotten vaccinated for the flu. And I don’t recommend it to my patients, but I don’t tell them not to get it, either. Personally, I tend to lean toward the conservative side for vaccines, erring on the side of less-is-more. (There may be reason for concern around excess vaccination in terms of increased risk for allergies, autoimmunity and other complex, chronic conditions.1,2) But should I get it? Should I recommend it? Will it benefit? 
 
In 2010 the CDC, but not the World Health Organization, decided healthy adults needed to be vaccinated. And by 2020, the CDC will want the lot of us (except those six months or younger) getting our annual jab.3
 
No other country is recommending influenza vaccination to healthy adults.
 
But here in the US, the urgency to be vaccinated for seasonal influenza has reached such a fevered pitch that some health care workers who choose against vaccination risk being fired or laid off. No longer will wearing a mask and washing hands — both of which effectively interrupt transmission --  suffice in some settings.
 
SO, armed with the experience of being a full-on participant in the 2012-2013 influenza epidemic, I dived into the research on the state-of-the-state of influenza vaccines. Yup. As I lay in bed, achy and chilled, I tapped out little search queries between cool sips of water....
 
 Here’s what I found: 
 
If we all believe the CDC regarding the influenza vaccine, will it become true?“The flu vaccine is the best way to protect against flu.” Nancy Cox, PhD, Center for Disease Control Influenza Division chief.5 
 
“Results for the 2012–13 season indicate that vaccination has reduced the risk for influenza-associated medical visits by approximately 60%, demonstrating the benefits of influenza vaccination during the current season.”6
 
But, “In the relatively uncommon circumstance of vaccine matching the viral circulating strain and high circulation, 4% of unvaccinated people versus 1% of vaccinated people developed influenza symptoms…. The corresponding figures for poor vaccine matching were 2% and 1%.... These differences were not likely to be due to chance. Vaccination had a modest effect on time off work and had no effect on hospital admissions or complication rates.”7
 
Commentary: We’re promoting the vaccine as our main-line intervention, and the early data coming out for the 2012-2013 flu season suggest there is a 60% reduction in medical visits.  (This doesn’t mean you won’t get the flu, it just might be less virulent. And the jury is still out on who will benefit from this reduction, healthy adults like myself who would otherwise whiz through the flu without issue, or people with chronic disease who won’t whiz though.) 
 
However, in 2010 a massive meta-analysis by the highly respected Cochrane Collaboration that I quoted above (looking at vaccine efficacy between the years 1966 and 2010 in 70,000 people), suggested that overall, the vaccine was woefully ineffective. At best, it reduced flu symptoms by 4%, and most likely it was more like 2%. They concluded that with the vaccine, you might get back to work a little bit sooner, but it wouldn’t reduce the risk for hospitalizations or developing complications like pneumonia. Thus, it seems healthy adults do better with the vaccine, rather than those who need it.7
 
Further, The Cochrane Collaboration included a warning label on the abstract. (I have NEVER seen a warning label on a research abstract. What’s next, the black box?) 
 
WARNING: This review includes 15 out of 36 trials funded by industry. (Four had no funding declaration.) An earlier systematic review of 274 influenza vaccine studies published up to 2007 found industry funded studies were published in more prestigious journals and cited more than other studies independently from methodological quality and size. Studies funded from public sources were significantly less likely to report conclusions favorable to the vaccines. The review showed that reliable evidence on influenza vaccines is thin, but there is evidence of widespread manipulation of conclusions and spurious notoriety of the studies. The content and conclusions of this review should be interpreted in light of this finding.”7
 
Commentary: Cochrane thinks their relatively puny, but statistically significant findings, might actually be inflated! This is because some of the studies Cochrane used were completed by the same folks who make the vaccines, who obviously have a financial investment in their studies being favorable.
 
But could Cochrane be biased? Some people think so. Dr. Michael Osterholm, director of the Center for Infectious Disease Research and Policy (CIDRAP), also released an exhaustive 160 page mega-meta-analysis just last year.8,9 (Download the full text free.
 
He thinks The Cochrane Collaboration’s meta-analysis eliminated some studies from their analysis that should have been included. Apparently, Cochrane’s results would be more favorable toward the vaccine with these additions. Dr. Osterholm’s group’s research was supported by grants rather than industry, so their work should be relatively non-biased. 
 
So, what then did Dr. O’s analysis have to say about the state-of-the-state of the influenza vaccine? CDC Megaphone
 
“The perception that current vaccines are already highly effective in preventing influenza is a major barrier to game-changing alternatives. Indeed, hundreds of influenza vaccine efficacy and effectiveness studies have been conducted since the 1940s, and vaccine efficacy in healthy adults of 70% to 90% is frequently cited. However, the preponderance of the available influenza vaccine efficacy and effectiveness data is from studies with suboptimal methodology, poorly defined end points, or end points not proven to be associated with influenza infection.”9
 
Ouch! So even though he challenges Cochrane, Dr. O obviously has some HUGE concerns around the current vaccines. Here’s what he had to say to the New York Times in November, 2012:
 
“We have overpromoted and overhyped this vaccine,” said Michael T. Osterholm, director of the Center for Infectious Disease Research and Policy, as well as its Center of Excellence for Influenza Research and Surveillance. “It does not protect as promoted. It’s all a sales job: it’s all public relations.” 5
 
Zing! 
 
Why can’t you swing a chicken without hitting an advertisement for the flu vaccine? They’re on every gas station, residence, warehouse, farmhouse, henhouse, outhouse and doghouse (and medical practice).
 
Well, for starters, there is some fear here. The flu could become serious business. In the 2009 influenza pandemic, the average age of death was 40 -- comparable to the 1918 pandemic. In all other pandemics, with the exception of 1918, the mean age of death was in the 60s and 70s, close to the life expectancy. In 2009 there were about 12,500 fatalities in the US -- much lower than all previous pandemics. The most vulnerable were obese individuals, children, pregnant women and those with asthma. (Attention integrative clinicians: we can assist these populations, can we not?). 
 
Scientists expect, for a number of reasons, that there will be another serious pandemic. If we’re not ready, we’ll likely see very high death rates.  Dr. O is pro-vaccine. When he mentions “game-changing alternatives,” as he does in the above quote, he’s talking about the current vaccine being insufficient, and wanting a new “universal” vaccine.  
 
But something more insidious is going on: a highly intractable refusal to acknowledge the limitations of our current interventions. I turn to two quotes included in Dr. O’s paper:9
 
“The greatest obstacle to discovering the shape of the earth, the continents, and the oceans was not ignorance but the illusion of knowledge.”
- Daniel Boorstin, 12th Librarian of the United States Congress from 1975 until 1987.
 
“For a successful technology, reality must take precedence over public relations, for Nature
cannot be fooled.”
- Richard Feynman, 1965 Nobel Prize laureate in physics.
 
Science, like the truth, is a delicate thing:  To the significant detriment of humanity, it can be squashed by fear, politics, policy, opinion and greed.
 
- Dr. Kara Fitzgerald, 01-22-2013
 
Epilogue:  I would be remiss in my duty as an integrative physician if I didn’t mention there are a plethora of tools to support the immune system before, during and after influenza. In fact, the integrative approach is urgently needed, given the likelihood of a major pandemic. In 2007 with the H5N1 scare, I published an in-house document for Metametrix Laboratory, addressing interventions for the bird flu that are generally useful, which I will link here. Also, for clinicians: The Institute for Functional Medicine’s 2011 annual Symposium was devoted to emerging infectious disease. Access The Challenge of Emerging Infections in the 21st Century. For everyone else, as I always say, talk to your neighborhood integrative doctor. They’ll help you! As you can imagine from this blog, my position on the vaccine hasn't really shifted...
 
1. Kondrashova A, Seiskari T, Ilonen J, Knip M, Hyoty H. The 'Hygiene hypothesis' and the sharp gradient in the incidence of autoimmune and allergic diseases between Russian Karelia and Finland. Apmis. Nov 6 2012.
 
2. Okada H, Kuhn C, Feillet H, Bach JF. The 'hygiene hypothesis' for autoimmune and allergic diseases: an update. Clin Exp Immunol. Apr 2010;160(1):1-9.
 
3. Control CfD. 2020 Topics and objectives: immunization and infectious diseases. Accessed 01-23-13, 2013.
 
4. Daniels TL, Talbot TR. Unmasking the confusion of respiratory protection to prevent influenza-like illness in crowded community settings. J Infect Dis. Feb 15 2010;201(4):483-485.
 
5. Pope. Reassessing the flu shot as the season draws near. 2012; http://well.blogs.nytimes.com/2012/11/05/reassessing-flu-shots-as-the-se..., 2013.
 
6. Early estimates of seasonal influenza vaccine effectiveness - United States, january 2013. MMWR Morb Mortal Wkly Rep. Jan 18 2013;62:32-35.
 
7. Jefferson T, Di Pietrantonj C, Rivetti A, Bawazeer GA, Al-Ansary LA, Ferroni E. Vaccines for preventing influenza in healthy adults. Cochrane Database Syst Rev. 2010(7):CD001269.
 
8. Osterholm ea. Influenza Vaccine Efficacy and Effectiveness: A Comprehensive Review. 2009; http://www.preventinfluenza.org/newsletters/101512_osterholm.pdf.
 
9. Osterholm ea. The Compelling Need for Game Changing Influenza Vaccines. 2012; http://www.cidrap.umn.edu/cidrap/files/80/ccivi%20report.pdf.
 
Photo credits: flickr.com, William Brawley, kazamatsuri
 
 

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