Monday, July 12, 2010

D-D-Depression

I was deficient in vitamin D. Of course. I paid attention to the official word about sunshine - it's bad for you. Ultraviolet radiation chops up your skin cell DNA, and with enough scrambled DNA and a bit of bad luck, you will eventually get cancer. There are several major types of skin cancer, but melanoma is the scariest, also, sun gives you wrinkles and age spots and... so I've been putting on sunblock and avoiding the beach except for a few days a year for a least 10 years.

At the same time the dermatologists and women's magazines were scaring us away from the sun, our own fat phobia and a cultural trend of eating less organ meat scared us away from the best dietary sources of some key fat soluble vitamins (A, D, E, and K). We don't want to be low in these vitamins, as they tend to help orchestrate a lot of functions in the body. Vitamin D (which is found in animal fats, but we tend to get about 90% from the sun) in particular seems to be involved in about 10% of the biochemical soupy stuff our body does every day. It has a lot to do with membrane signaling and scavenging up any screwy cells that are starting to go awry (i.e. cancer), and being low in vitamin D seems to put us at hugely increased risk of cancer, including melanoma. And prostate cancer. And breast cancer. And colon cancer. In fact, women diagnosed with breast cancer in the summer and fall have the best prognosis. There are reports of chemotherapy not working as well in the winter. (1)

There are also links to mental health - depression, bipolar disorder, and psychotic disorders (2) have all increased in populations once most people stopped working outside and went to work inside. The elderly with low vitamin D also have much higher rates of depression (3). In this study of bone mineral density and depression, the elderly with poorer bone status were also more depressed (vitamin D was not explicitly stated to be the possible linking factor for both illnesses).

How would vitamin D affect the brain? Vitamin D is involved in the synthesis of the catecholamines (which are highly involved in neurotransmission). Summer sunlight increases brain serotonin levels twice as much as winter sunlight (4). Neurons and glial cells in all kinds of areas of the brain have vitamin D receptors on them, indicating a brain that is hungry to use vitamin D. Some effects in the nervous system include the synthesis of neurotrophic factors (what I call "brain fertilizer"), inhibition of the creation of an enzyme that chews up nitric oxide, and increasing glutathione levels. (See my previous posts for a molecular description of how some of these brain chemicals are thought to be involved in depression). As vitamin D in the periphery is associated with scavenging and cleaning cancer cells, vitamin D in the central nervous system seems to be involved in detoxification and anti-inflammatory pathways (5)(6).

Does supplementation help depression? Well, the first several studies were disappointing. Harris and Dawson Hughes tried treating Seasonal Affective Disorder with 400 IU vitamin D2 daily. Didn't do squat. Of course, D2 is the plant form of vitamin D (the animal form is D3), and 400 IU is a tiny dose anyway. Lansdowne and buddies gave 400 IU and 800 IU of vitamin D3 to healthy subjects in late winter, and found a lightened mood in those receiving the supplements. Hollis gave people with seasonal affective disorder a single 100,000 IU dose of D3, and found it to be more effective than light therapy, and the improvement was statistically correlated with the improvement in serum 25(OH) vitamin D levels. In this intriguing study, young adults were given access to tanning beds on Mondays and Wednesdays. One bed had UV light, and identical bed didn't. On Fridays, the participants were allowed to choose which bed they wanted. 95% of the time, they chose the UV bed, and participants also reported being more relaxed after a UV tan than in the sham bed.

Unfortunately, there is no large, well-designed study of D3 supplementation for depression that I'm aware of. However, there is enough interesting evidence for such a trial to be done, especially in populations that are more likely to be vitamin D deficient, such as the elderly. Like fish oil, vitamin D3 is cheap (about $10 for a three month supply) and readily available. And given the links to other diseases also (heart disease, stroke, osteoporosis, kidney damage, hypertension, you name it (1)), it would seem prudent (and money-saving from a public health standpoint if a lot of cancer is really prevented by adequate supplementation) to test for and treat deficiency in people with psychiatric disorders.

Another issue is that the RDA for vitamin D is woefully small. About 400 IU daily. This is an amount that will keep you from getting rickets, but it's certainly not an optimal amount for humans. I've heard murmurings that the official RDA is going to be increased to 1000 IU daily, and most decent multivitamins will have 1000 IU of vit D already (that's why your multi says "250%" of RDA of cholecalciferol (vit D3), in case you were wondering). The amount in fortified milk is also small, so that one would need to drink a truckload for it to matter much.

So how much vitamin D do we need, and hey, isn't vitamin D a fat soluble vitamin, which means we can store is for a long time, and couldn't we get toxic from high amounts? The answer is - we probably need many times the current RDA for vitamin D to get reasonable serum levels of the stuff, and yes, we can get toxic, but for most people that is not a realistic worry.

According to the Vitamin D Council, a serum level of 50 ng/ml or higher of 25 (OH) vit D3 is optimal. This level is not without controversy, and 35 is accepted by most as the minimal acceptable level. One probably doesn't want to go above 100, though toxicity has only been reported at serum levels higher than 150 (6). You can't get too much vitamin D from the sun - our skin actually destroys excess vitamin D made there after you have enough for the day. A cool regulatory mechanism if ever I heard one. You *could* theoretically get toxicity from combining high amounts of supplementation *and* lots of sunshine. There's a description on the vitamin D council website of one guy who actually did get toxic from supplements - turned out an industrial accident made his particular variety of vitamins (Prolongevity) contain up to 430 times the amount on the label. This guy was taking between 50,000 IU and 2.6 million IU daily for about two years. He recovered (uneventfully) with some medicine and sunscreen.

So how do you know if you have enough vitamin D? Well, if you are a lifeguard in Miami, you're probably fine. If you have very dark skin, unless you are a lifeguard on the equator, you probably need some supplementation. It can take someone with very dark skin about 5-6 times longer in the sun to get enough vitamin D to have adequate levels compared to someone with very pale skin. If you live north of 40 degrees latitude (above New York City), you only have a few weeks in the summer to expose that skin and get the full amounts of vitamin D you need to last you for the year, and you may have to supplement (again, there is controversy about this, especially as very pale people of Northern European ancestry seemed to live to the far north of 40 degrees and had only a few days a year they could possibly get adequate vitamin D from the sun). Anyway, to really know your blood levels of vitamin D, you need to get a blood test. The key level you need to know is 25-OH vitamin D3. If your doctor orders 1,25 OH or just "total vitamin D" you might not get the right number, so make sure you look at the lab slip. If you don't want to go to the doctor, you can go to this website and pay $65 or so for a home testing kit. Unless you live in New York state, where home testing via mailing bloodspot cards is apparently illegal.

So let's say you ordered a home test kit and stabbed your finger and shipped your spot of blood back to the lab and your level comes out to be 31 ng/ml. There's a general rule of thumb that 1000 IU of supplementation daily will increase blood levels by 10 ng/ml. (Use geltabs in oil suspension rather than tablets, unless you are always going to be taking the supplement with some oil/fat.) So let's say we are aiming for 50 - then one could take 2000 IU D3 daily in the morning. If you were already supplementing at 1000 IU (in your multivitamin, for example), you could take an additional 2000 IU daily, and you could skip the additional supplementation on days you spent time in the sun (without suncreen - sunscreen will block the UVB rays that synthesize vitamin D in the skin). Arms and legs exposure for 20 minutes midday in the summertime in Boston about 3-4 times a week would get you a goodly amount (probably around 10,000-12,000 IU with each exposure) if you have pale skin. That kind of exposure is not such a big deal for skin cancer risk, as long as you avoid burning. The farther south you are (until you get to the equator, then reverse!) and the paler you are, the less time you need.

It is standard practice for physicians to treat vitamin D deficiency with 50,000 IU pills once a week for 8-12 weeks, then recheck. Unfortunately, a recent JAMA study of similar treatment in elderly women (admittedly it was 50,000 IU D3 daily for 10 days) resulted in a great increase in the number of fractures. The editorial for the study thought 4000 IU daily was a safer, more physiological amount to treat deficiency, and be sure you are getting adequate calcium too. However, if you supplement with calcium and vitamin D3, as your vitamin D levels become adequate, your absorption of calcium can increase quite a bit (see slides 18-36). Therefore, you may not need as much calcium if you take vitamin D. The recommendations are not set in stone, though. (Our current RDA for calcium may be high simply because we don't get enough vitamin D!) Also, most of the prescription vitamin D doses are D2, not D3, and D2, the plant form, is probably not nearly as effective as the animal-derived form, D3.

Here's yet another thing to watch out for with higher-dose vitamin D3 supplementation. Occasionally, you will unmask some hyperparathyroidism. If someone's parathyroid is working on overdrive, he or she will start to have serum levels of calcium that are way too high, potentiated by the higher doses of vitamin D3. This can be dangerous if it goes undetected, though high calcium levels can be very uncomfortable, with symptoms of muscle twitching, cramping, fatigue, insomnia, depression, thinning hair, high blood pressure, bone pain, kidney stones, headaches, and heart palpitations. Since bone pain, fatigue, depression, and insomnia can be symptoms of low vitamin D3 as well, it is important to realize that if your symptoms get worse with supplementation, you should see your doctor and get a calcium and parathyroid hormone checked. While I personally don't check calcium levels with the initial vitamin D level, I do check it for follow-up ones (I tend to check after three months or so). While home testing is a neat option for the initial level, seeing your doctor about follow up and his or her suggestions for supplementation is a good idea if your level is found to be low.

And what about those other fat soluble vitamins: A, E, and K? It is important that you have enough of each of them, or things can get a bit screwy. For example, in order to create bone, you need adequate vitamin D (at least a level of 20-30), adequate calcium, AND vitamin K2. The best sources are animal fats, particularly the fats from animals that eat their natural diet - grass for cows, or grubs and grains and whatnot for chickens. So pastured chicken egg yolks, and butter and liver from pastured cows. Conventionally-raised eggs can have about 1/20th the vitamins of pastured eggs, and butter from grain-fed cows may have as little as 1/200th as much K2 as pastured butter, so it really does matter what the animals you eat ate. Vitamin A is also found in multivitamins and it is important not to have too much vitamin D3 and too little A, so I've recommended a multivitamin in addition to vit D3 for people who are deficient in serum 25 (OH) vitamin D (and aren't big liver eaters :)).

Strict vegetarians - here's another place you need to be super careful about what you eat, and you might need to choke down some fermented soy products (netto) to get enough Vitamin K2. K2 isn't found in a standard multivitamin (though we can make K1 into K2, if our intestinal flora is happy, which it might not be on a standard American diet - no idea about flora in a vegan diet. Interesting question) and is vital to bone formation and in keeping our arteries resilient. K2 is what warfarin blocks, so don't take it if you are on coumadin for blood clots. (Though why are you at risk for blood clots in the first place? maybe too much omega 6 compared to omega 3??)

So, a key part of good, lasting health is either to get plenty of (safe - no burns!) sun as our ancestors did, or use today's science to get your blood levels of vitamin D where they need to be. Chat with your doctor about it - and check out the Vitamin D Council Website for more information.

3 comments:

  1. Interesting stuff...I need to read through again to digest all of that info. Do you recommend the average person have their vit D levels tested? Or is it safe to assume that most people are deficient to a certain level?

    I wish I could get my DVT specialist to read some of these posts - I asked her about food/weight affecting DVT risks and more specifically about Omega 3-6 ratios and she just gave me this blank stare... Guess that answered my question about her knowledge of that. I know Drs are very busy and such...but it was a bit disappointing.

    Can an out-of-whack O6-O3 balance cause elevated anti-cardio lipins??? (not your specialty...I know...) I wish I knew more about blood and arteries and how those things worked a bit better.

    I have a request for a post if you run out of things to write about. :-) Cholesterol - what all of the levels mean; what the healthy ranges are, etc. I'm sure I could google it, but you do such a great job of explaining things for the non-doctor that I thought I would ask.

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  2. Laura - To be honest I'm of mixed opinions about lab testing in general. For most people, the labs don't matter if you recommend the same healthy interventions no matter what the lab test says... vitamin D may be the exception, as we are simply not out in the sun as we used to be, and we are supposed to make vitamin D in our skin, and oral D3 is the same thing as what is made in our skin once the liver is utilized to metabolize the whole thing. The closer we live to the poles, the more important it is to test - grassroots health recommends supplementing with 2000 IU for three months, then testing. They don't have a test for calcium, though, just the (25) OH vit D3. And, unfortunately, your doc may not know much about vit D at all. I've seen docs order the 1,25 (OH) vit D test which is completely useless. Fortunately the labs usually throws in the 25 (OH) vitamin D tests to save us from ourselves....

    So far as the DVTs, I can't give personal advice, but obesity is definitely associated with increased risk of DVT (I don't have a reference for that - I figured it was common knowledge among doctors), and I'm going by the basic biochemistry to suggest that O6/03 ratios are important for clotting, as 06 is a precursor for thromboxane (aspirin works by inhibiting the production of thromboxane), among many other inflammatory things (wikipedia always has embarrassingly good articles about sciencey stuff - http://en.wikipedia.org/wiki/Eicosanoid).

    So far as anti-cardiolipin antibodies, you are right, I don't know much. It sets off my "autoimmune" flag, which sets off my "crazy out of whack inflammation and why the heck would that be happening" flag - which always brings me around to weird antigens causing systemic problems (the most obvious sources would be dietary or infectious), and fired up immune system (could happen from infection or perception of attack - i.e. antigens or stress reaction). Did find this interesting article linking inflammatory bowel disease and anticardiolipin antibodies - http://qjmed.oxfordjournals.org/cgi/content/full/95/4/253-a

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  3. As to the cholesterol post, I can certainly throw some stuff up there, but my views on cholesterol are rather shockingly unconventional, so I'm not sure how helpful they will be to the general public. I believe certain kinds of elevated cholesterol are a sign of inflammation, and it is useless and perhaps dangerous to treat a number when we ought to be honing in on the cause of the inflammation. Checking everyone's cholesterol all the time has enriched the pharmaceutical industry, but has it decreased heart disease?? That is a billion dollar question.

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