Homeopathic Vitamin D Not Effective for Depression

Last week, amidst all the news fall-out over that egg study, Lance Armstrong, and Neil Armstrong, a few other studies were noted that have some EvPsych relevance.

Here is a music selection for the Sunday morning reflective crowd: Chopin's Ballade No. 4

And let's just get it over with:  Vitamin D Supplementation and Depression in the Women's Health Initiative Calcium and Vitamin D Trial.

Okay, HUGE double blind randomized controlled trial.  Over 36,000 women, randomized to placebo or 1000 mg calcium + 400 IU vitamin D3 daily for 3 years.  Depression scores were measured via questionnaire (one I've never heard of, the Bernam scale) and antidepressant use (maybe problematic because different classes of antidepressants have varying uses, for example, TCAs are prescribed for migraines and chronic diarrhea, and SSRIs are used for anxiety) at baseline and several follow up points.  In addition, a subset (828 women) actually had D levels measured during the trial.  Beginning average level was 52 nmol/L which is about 20.8 ng/ml in the units I will typically see on a lab report form.  After two years (and measuring a separate group of 400 some-odd people), the average level in the supplemented group was 28% higher than those who were not supplemented. (Assuming a similar 20.8 ng/ml starting point, two years of D supplementation increased levels to 26.6.)

Kinda scary that the average level of these women at the beginning is just a tick north of absolutely deficient even according to the conservative Institutes of Medicine.  400IU does seem to prevent rickets, and it is similar to the amount of oral vitamin D one might be expected to get from eating cold marine animals.  But it certainly doesn't make up for recommending the entire population avoid the sun at all costs.

In the end, supplementation with 400IU Vitamin D3 (and calcium) was associated with an increased chance of reporting depressive symptoms (the odds ratio was 1.16, though, not too terribly exciting) and not associated antidepressant use compared to placebo.

I'm not surprised, and I'm somewhat annoyed with vitamin D studies and depression at this point.  Studies tend to use teensy levels or enormous ones (and please see that link for a round-up of the relevant D and mental health studies.)  Why don't we find a middle ground between 400IU and 500,000IU (literally)?

I'll share my clinical experience, which, being anecdotal, may not be worth much.  I've been more aggressive about measuring vitamin D in the last few years (as have the internists I work with), and I would say roughly 1/3 of the folks I measure (or have had a D measured in the past year by the primary care doctor) are absolutely deficient.  Meaning below 20 ng/ml.  Levels between 10-15 are common, but I've seen 4s and 8s as well.  The super low folks have tended to have a "sick" look: pale, circles under the eyes, bloated, tired.  (Though not everyone who is pale and tired has a low D by any means!) If I had to guess from just looking at them, I would think they might be fighting a cold or were hypothyroid.  Most of the time, the thyroid function is absolutely normal.

Most of the folks I see have depression, and typically some sort of resistant depression, and I would say 99% of people come to me having already been put on psych meds of some kind.  It's a bit hard to generalize, each patient has his or her own particular circumstances, character strengths, education, and external stressors… but I've figured out that some long-term patients with ultra-low vitamin D finally responded to all the psychiatry mucking around (bolstering supports, lifestyle interventions, therapy, medication adjustment) after the D was corrected.  Shorter term patients have looked better and done better since getting D out of the basement.  I've never attempted an isolated D intervention (which wouldn't be standard of care by any means).

So, while resistant depression generally requires a lot of adjustments in different areas of life to get trending a better direction and to get people more functional and happier, I surmise that replenishing super-deficient vitamin D may be one of those adjustments that ought to be done and likely won't hurt, and seems to be a piece of the puzzle out of place in resistant depression.  Knowing the role of vitamin D in the nervous system so far as inflammation reduction and neuronal repair, there's a sensible mechanism at play as well.

Another interesting bit to the D replenishment story… in the past two years, four of my patients have developed high calcium with adequate D supplementation to bring the levels above 20 ng/ml.  Three of them were found to be hyperparathyroid, and parathyroid tumors were found and later removed, resolving many of the original psychiatric complaints.  The fourth patient is still undergoing a work-up but since a lump was palpated on the parathyroid, it is likely she has a tumor as well.

When I was in medical school, surgeons absolutely loved parathyroid cases because they were relatively rare.  I don't know if four patients in two years is another anecdotal anomaly for me, but I do measure calcium along with vitamin D, and if the calcium pops above 10.2 with supplementation, I'm very quick to refer the patient back to the primary care doctor for further work-up.  Having seen so many cases so recently, I wouldn't recommend supplementing a super-low D (particularly below 20, which is low enough that hyperparathyroidism can be masked by the low D level) aggressively without measuring calcium along with it.  If you have normal levels (say 30 or above) moderate supplemention of 1000-2000 IU daily is probably fine, because if you had hyperparathyroidism, you would already know it, but keep measuring.

Ancestral Health Symposium 2012 -- The People Post

POP ETC Keep It For Your Own.  Right click to open in new window.

So I had a great (but very tiring) time at AHS12.  In fact I was useless for about 36 hours post-event, with the extra day making it a bit grueling compared to last year, but part of that was entirely my own fault for staying up so late on multiple days.  It was nice to catch up with the personalities and folks and meet all sorts of new ones.  I'm definitely going to miss some folks and for that I apologize in advance.

I was delighted to spend some quality time with:

Mark Sisson:  I was fortunate enough to spend nearly an hour learning a bit more about Mark and his history of athletic endeavors, and how he transformed his experiences and success with primal eating into his Primal Blueprint, and a bit of what his motivations are.  As I mentioned in the last post, most people have an angle.  My disclosure is my paid blog over at Psychology Today, for example.  For the most part, this blog has been a very expensive but fulfilling hobby.  That will change soon when I will make an exciting announcement.  And sure, Mark wants a successful business, but it is also extremely important to him to help folks eat better and live better.  He has always done a good job advocating for balance and common sense.  I've heard him say multiple times… the goal is not to get the body of a Sports Illustrated swimsuit model.  It's to be happy and healthy, and *not* to be obsessed with food.  It's to eat well in such a way that you don't have to spend so much time thinking about it, counting, or carrying around little snacks to eat every three hours.  It's to be able to tolerate a fast every once in a while if you are traveling and there's nothing that good to eat.  It's to eat well most of the time so that you can enjoy champagne and cake at your great aunt's 100 birthday party (barring alcohol problems or wheat allergy) without worry or recrimination.  In any event, Mark is good people and it was a great pleasure to get to know him better.

Stephan Guyenet: I really enjoy talking with Stephan each time I have the opportunity.  He's thoughtful, careful in his writing, and an exceptionally kind person.

Chris Masterjohn and Denise Minger: We were able to talk a bit about Chris' successful defense of his dissertation (on a topic I have a great deal of interest in, certain specific aspects of glutathione metabolism) and Denise's writing project.  They seemed a bit more relaxed than others at the conference, maybe because Chris got that PhD...

Chris Kresser:  Somehow each time I talk with Chris I tend to be fired up about something, so I'm not sure the impression he has of me!  He understands the dilemma of a clinician, that things aren't always so simple, that lab tests aren't always accurate, and that the answer isn't always more supplements or less sugar or whatever the paleo flavor of the week is.  I'm always eager to see his new writings and ideas.  It's also nice to talk shop about babies and parenting.

Rick Henriksen MD, Catfish MD, Primal Mountain (Jacob Egbert, DO), Vlprince, and Dr. Lucy:  I can't say enough about this crew of doctors.  We were pretty much inseperable during the event, and various folks did everything from help me with my sinus infection, share chocolate, phone chargers, buying dinner, introducing me to all sorts of great practitioners, and even bringing me farm fresh rendered lard and putting me up for a couple nights in town so I wouldn't have a 45-90 minute commute each way.  The three day event would have been nearly impossible without their support and company.  I love them all a great deal and can't wait until we all meet again.

My sister in law, an emergency room nurse who volunteered for the event and by the end seemed to become friends with everyone.  (And a special thanks to my husband for wrangling the kids alone as he is always happy to do when I'm away for these shindigs.)


I had a few moments (and would have loved to spend more time) with:

Ned Kock, Beth Mazur, Paul Jaminet, Keith and Michelle Norris, Basil G, Aaron Blaisdell, Jamie Scott and Anastasia Boulais, Grayson Wheatley, Dallas and Melissa Hartwig, Kamal, Don Wilson, Lindsay, Colin Champ, and Squatchy and countless others.

Someone I would love to chat with more, but I figured it would take some time to do it justice and he was always mobbed:  Robb Wolf.  One day, maybe!

Finally, I wanted to address some concerns that have come up on the Internet about our physician's forum.  Some great practitioners (chiropractors, RDs, nurses, etc.) felt left out because our little endeavor is for MDs/DOs, medical students, and the international equivalents.  We think other practitioners are terrific, incredibly valuable, and certainly have skill sets we do not possess, and an eventual plan would be to have several nested forums with all clinicians and researchers or whoever able to share ideas, grant funding, experience, resources, etc.  Our forum is quite small at the moment and is focused on addressing specific concerns and needs of physicians, having to do with medicolegal questions, evidence-based practices, case studies, etc.  For various legal and traditional reasons, this model can only work with a confirmed set of physicians.  We're not trying to be exclusive or leave anyone out because we are jerks.  This model meets our current needs and we hope to collaborate with all kinds of practitioners in the future.

There has also been a lot of discussion about AHS12 and the quality of speakers, the lack of diversity, and the judgmental atmosphere.  I felt the speaker list was more diverse than last year, and interest from many ethnic groups is growing.  These events filled with nutrition fanatics and folks who work out for a living is always a bit of a beauty spectacle.  Many folks get into evolutionary styles of eating and living for reasons of vanity (hey, I did…).  I'm not perfect by any means, being a middle-aged mother of two, but I personally felt comfortable and that people weren't judgmental to my face, though I'm not going to be walking around the AHS in spandex any time soon.  Its unfortunate that others felt judged or uncomfortable or excluded.  I thought the talk by Dr. Eaton about ageing gracefully living a paleo lifestyle was a nice antidote to the youth obsession… but I'm one of those folks who generally assumes others are thinking kind thoughts and giving people the benefit of the doubt, so maybe I'm not the best one to judge these sorts of things…

Jacob Egbert and Rick Henriksen

Don Wilson

Catfish

Victoria Prince and Lindsay Starke

Me, relaxing in New Hampshire a few days after the conference

Well, opinions and criticisms are useful, particularly if they lead to reflection and self-improvement.  Real time evolution, if you will.

AHS12 as a Practicing Clinical Physician

This past weekend I had the terrific opportunity to attend the Ancestral Health Symposium 2012, and also speak to a much larger audience than I could have anticipated.  I'd been to the original symposium in LA last year, and got a real sense of how much the interest in ancestral health lifestyle has grown in such a short period of time.  I'll probably gossip a little more in a later post, but for now I wanted to give some of my personal ideas inspired by the excellent post of Paleolithic MD, a Physician Manifesto.

Last year, I was thrilled when two physicians came up to me and we were able to talk a bit of ancestral health shop.  Sometimes being a Western physician interested in ancestral health principles can feel incredibly lonely, exhilarating, and even frightening.  In March I went to PaleoFx and met a core group of family medicine and physical rehabilitation physicians from Utah who wanted to organize a physician's forum.  We bonded immediately, because we have such similar experiences and goals that are not exactly shared by anyone who has not tried to juggle the practice of clinical medicine and evolutionary medicine principles.  Doctors have particular needs, obligations, regulations, and a widely varying patient base, ranging from those who are very ready to make healthy diet and lifestyle changes and those who will continue to smoke while dragging around an oxygen bottle.  

Everyone comes to see a psychiatrist from a different place in life.  I might not talk too much about diet for months or years of working with someone because we are working on keeping someone employed, brainstorming about how to keep from being homeless, or working on how to keep from self-injuring, drinking, or suicide.  Sometimes folks embrace dietary and lifestyle changes as a part of a solution to these enormous problems, but sometimes they cannot or will not… and some may come to me years later and begin to ask about nutrition or sleep, but many, many folks never will.  With very few exceptions, I do not kick people out of treatment just because they don't follow my advice.  Nor can I judge when someone with particular temperament, education, family situation, and stress is not prepared to make major lifestyle changes.  I don't live in anyone's shoes but my own.

After PaleoFx, the Utah docs and I began the embryonic stage of a forum for MDs, DOs, and medical students, and at AHS12, put out a call for other physician attendees to come and talk about joining forces for support, education, and other practical considerations.  Rick Henriksen, MD, on faculty at an academic medical center in Salt Lake City, has done a great job putting together statements of basic principles and ideas.  While AHS11 had a great introductory and research focus that was expanded into AHS12 to include even more anthropology, different angles on the science, and some of the old tired arguments about whether glucose will kill you or not.

We were all surprised when 30-40 people, mostly physicians, showed up, interested to network and learn.  Of course one travels to a conference to network and learn, but I hadn't realized there were quite so many physicians in the "fold," as it were, and if there are this many physically attending the conference, how many are now out there in the community or academia?

Doctors for the most part do not want to burn down the academic medical center.  We want to integrate the best sensible practices of Western medicine and ancestral health principles.  While everyone (including me) can bemoan the number of C-sections and the (lifelong?) alterations in microflora that might involve for the infant, I was seated between two very amazing doctors, both born by C-section, who might very well have perished along with their mothers at birth without the intervention.  I've seen midwifes claim rates as low as 2% C-section, and the near 30% rate in the US is no doubt too high, I don't know that anyone who cares for women and babies who would say the C-section rate should be 0%.

The clinical medicine place where allopathic and ancestral health principles meet is in proper nutrition, preparation, and education to help a mother be as healthy as she can be prior to conception and pregnancy and to avoid some of the complications that may increase risk of C-section (such as obesity, gestational diabetes, or hypertension).  But again, some women won't or can't make the changes that could ameliorate these complications, and sometimes the changes simply aren't enough.  Then the key is to be educated and experienced in childbirth to minimize unnecessary intervention, and to know when to act decisively if a vaginal delivery is not possible.

Often antibiotics are overused, but sometimes, if you don't take antibiotics, you will hasten your death or end up with a disfiguring surgical wound infection.

Physicians must navigate the evidence, plausible biologic mechanisms, unknowns, and various corrupting or biasing influences.  There is the industry money from pharmaceutical companies or supplement companies or shoe companies or traditional entrenched methods that may have no basis, personal pride or narcissism that might make the doctor recommending pig thyroid for everyone seem like a convincing plan, but ultimately the harms may outweigh the good.  There is a mountain of information to negotiate and the motivations of the presenters of the information to consider.

And sometimes there are health problems that can't be changed, but only borne.  Supporting someone in coping can be the physician's most valuable skill.  It is perhaps the oldest one.

As far as the practical implications for ancestral health in the western medicine paradigm today and in the future, I'm most excited about the potential for widespread support of a whole foods, anti-inflammatory, processed-foods restricted diet, and the end of academic dietitian and nutritional support of micro nutrient-poor and then enriched processed foods as "health food."  I'm also interested in the possibilities of immune modulators such as helminths and pseudocommensials for autoimmune disease, and learning more about how technology use affects sleep and mental health.  Other things, such as being on the lookout for iron overload and encouraging regular blood donation, particularly for men, and learning how to avoid toxic imbalances of nutritional supplements while using them judiciously to replete deficiencies will continue to be practical yet tricky.

With all the tinkering, in Western medicine and in ancestral health, we don't want to lose sight of the basics.  Now matter how healthy I make today, I can't undo the sleep-deprivation of the past weekend.  No matter how many times I quantify hormone levels with lab tests, I can't get your hypothalamus and testicles or ovaries or adrenals to work together if you don't help them out by eating and sleeping and laughing enough.    

I'm excited about the future collaboration of evolutionary-minded doctors.  Now, getting doctors to agree on much of anything can be like herding cats, and establishing some maverick (but very sound!) principles in the age of increasing pressure for evidenced-based medicine to be cookie cutter medicine delivered from a manual can seem daunting.  As doctors, however, the first thing we must remember is to meet the patient where he is.  If we start there, it is much harder to fail.  Our job is to exemplify, as best we can, good principles of healthy living and to deliver support and healing.  We will do a much better job integrating the best science of modern medicine and the sensible, proven traditions and experiences of our human past.

Mainstreaming

For all that I have a jabbery twitter account and like putting filters over my crap pictures for posting on instagram, I'm not exactly the kind of person that when you meet me for the first time, I'll say, "HEY, HAVE YOU SEEN MY BLOG??"

In fact, many of my friends and patients don't even know I have a blog.  It's sort of a niche audience.  But as the years go by and the archives build, more and more I will talk to a colleague or therapist who might refer to me, or even someone at the gym, and they will say, "Oh, by the way, I saw your blog…"  

The colleagues are especially exciting.  In the past few months I've been invited to a few more journal clubs and Grand Rounds to speak to more psychiatrists, neurologists, and other head-interested professionals.  Some of these folks might even have a research budget.  I really love these opportunities, because when it comes down to it, Evolutionary Psychiatry is not about the paleo diet.  It's about the pathology of mental illness and conceiving our brains as connected to our bodies and guts and environment.  It's about how physical and mental health are derived from our genes and the protoplasm of the world around us.  It's about simple interventions and the complex ways in which they influence our nerves and hormones and flesh.

It's a niche audience, but I feel Evolutionary Psychiatry deserves to be mainstream medicine.  It's about asking questions in a common sense fashion, and approaching disease with multi-pronged, inflammation-reducing and neurotransmitter-savvy and sensible solutions.  It's about acknowledging the wisdom of the past generations and translating the therapies and traditions into real results.  Mostly it is about asking the questions in a way that will generate the answers we need for the science to be useful.

My daughter asked me if the iPhone knew everything.  I said, a vast amount, no doubt, if you ask the question just the right way.  She will never remember an early life without Siri.

I didn't plan on blogging today, but in my mailbox arrived the brand spanking new fresh edition of the Green Journal, and two of the articles just SING evolutionary psychiatry.  So here I am again.

A Silent Film: Danny Dakota and the Wishing Well (reminds me of those angsty John Hughes movies from the 80s, before he started doing movies about John Travolta and babies)

The first article is a double-blind placebo controlled trial of NAC in cannabis-dependent adolescents (1).  I know there is a bit of a link between paleophiles, libertarians, real food hippies, and weed, but I've never been a big fan.  Mostly because I'm often confronted with parents and older adolescents who struggle with psychosis and/or lack of motivation and crippling anxiety who smoke pot ALL THE TIME.  Not to mention the older folks who come in after decades of daily heavy use and can barely finish a sentence.  I've covered it before here and here.  Weed has some interesting properties, no doubt, but I've seen it to be more the fountain of rotten brain, agoraphobia, and dementia than the fountain of creativity and youth.  My sample is not randomized, and I have no doubt of that.  But roll the dice and take your chances, as they say.

ERGO, I think finding ways to get adolescents to smoke less pot might be a good thing.  And in the linked paper, it is noted that 25% of high school students use pot, 7% on a daily basis.  Besides standard psychosocial therapies, there's not much out there to help adolescents quit the dependency.  Could a pill help?

NAC, as we know, is particularly exciting in psychiatric disorders because it targets glutamate and antioxidants in a novel way.  There's no prescription pharmaceudical with the research data or similar mechanism.  In animal models, self-administering addictive drugs down-regulates the cysteine-glutamate exchanger in the nucleus accumbens.  NAC upregulates this exchanger, reducing the reinforcement of drug-seeking.

The authors of the study did a promising open-label pilot trial and then organized a larger randomized controlled trial.  Cannabid-dependent adolescents (13-21) who desired some help and met other exclusionary criteria were randomized to placebo or 1200mg NAC daily for 8 weeks.  All participants received cessation counseling at every research visit.  Cannabis use was determined by urine sample (which will be positive for about a month with moderate cannabis use, depending on body habitus).

In the NAC group, 40.9% of the cannabis tests were negative (assuming all missed urine tests were positive).  In the placebo group, 27.2% were negative, a statistically signficant difference.   Participants who had made the decision to quit and were negative at baseline were six times more likely to be abstinent through the rest of the study, those with fewer years of use were more likely to be negative, and those with major depressive disorder were more likely to continue using.  There were no significant differences in adverse events between NAC and placebo users (like most studies, NAC users had fewer side effects than placebo, 38 in the NAC group and 46 in the placebo group).

These results should be repeated and consolidated at multi-treatment center groups, but all in all it adds to the NAC family of interesting psychiatric results.

The Ting Tings Hit Me Down Sonny

The second interesting article is about poor nutrition at age 3 and schizotypal personality at age 23.  Studies of populations in China and the Netherlands have shown that periods of famine during pregnancy results in the birth of children who are twice as likely to have schizophrenia or schizoid personality, and the risks can be worse when malnutrition extends to the postnatal period.  Thinness in childhood from malnutrition is associated with later schizophrenia as well.

Is it the malnutrition or some other variable that increases the risk?  Malnutrition is associated with low IQ, and low IQ is also associated with the development of schizophrenia.  Iron deficiency is associated with malnutriton, stunting, and schizophrenia.  Let's try to sort it all out…

In Mauritius, all children (1795) from two towns born in 1969 to 1970 were followed from the age of three.  Height (in developing countries, a measure of nutitional status) and hemoglobin (which is an indirect measure of iron) were collected and normalized for the different ethnic groups.  An "adversity index" was also measured from a home visit for each child, counting points for uneducated parents, semiskilled parents, single parents, separation from parents, large family size, poor health of mother, teenage mother, or overcrowded home.  IQ was measured at age 11.  Schizotypal personality was measured with a questionnaire at age 23.

The researchers found that poor nutrition in early childhood resulted in poor cognitive performance (IQ at age 11) and a higher risk of schizotypal personality at age 23.  The adversity index at age 3 was also significantly related to IQ at age 11.  Individuals with higher performance (vs. verbal) IQs were less likey to have schizotypal features.  It is thought that malnutrition leads to hippocampal and frontal brain impairments, leading to difficulty with emotional regulation, maintaining relationships, and the all important executive function.

How do these finding play in the first world?  I suppose it depends on how many pregnant young women live off of vending machine food.  Still, more evidence that nutrition is important.  As if we didn't know.