Zinc Picolinate Research Paper

Zinc is one of the longest-studied nutrients that correlates with statistically significantly less acne. Some months ago, I discovered that around 200mg/day of zinc picolinate could, under some circumstances, make me dramatically acne-free for the first time ever. That led to a very long course of study, research and experiments.

For a megadose of zinc to affect acne dramatically, a good bet was that zinc is a cofactor in a reaction that affects acne. If you have a chemical reaction in the body like Zinc + X -> Y, then flooding the area with zinc will at least modestly increase the production of Y, since it makes it more likely that all the available "X" will get used up. After much study, I concluded that "Y" is actually zinc superoxide
dismutase, or ZSOD. ZSOD comes with the usual labels people grope for in acne cures: anti-oxidant, anti-inflammatory, etc.

But then, what is the "X" that must be combined with zinc to make this reaction? If I have to overdose on zinc to get enough "Y", the implication is that what I'm really deficient in is "X". Like most people in America who eat meat, it's highly unlikely that there is any lack of zinc in my diet. If I could remedy my deficiency in "X", then I should be able to be acne-free without taking any zinc.

More study led me to conclude that "X" is melatonin. Melatonin slows cell division. It may decrease the production of androgens right in the skin. And perhaps most importantly, melatonin crosses the cell membrane and directly stimulates your DNA to produce the precursor to ZSOD, the molecule that zinc must combine with in order to create ZSOD.

Experiments with melatonin were immediately fruitful. By tending to my sleep cycle, I was soon able to be acne-free on less zinc, but still could not be acne-free reliably for long periods without any zinc supplement. Something was still missing.

The final piece of the puzzle was finding the fairly recent discoveries that show that, in modern life, we fail to effectively suppress daytime melatonin because we live in relatively dim indoor light. When you don't effectively suppress daytime melatonin by having your eyes in outdoor light all day long, two bad things happen. First, your gut thinks it's nighttime and you get carbohydrate malabsorption that keeps it from effectively digesting tryptophan (the fuel your body needs to make melatonin) and (tada!) zinc! Second, you get a "flattened" melatonin curve when you sleep at night -- your body simply doesn't produce the giant burst of melatonin at night that nature intended. The data fits this hypothesis nicely, including the most obvious points:
Do low zinc levels correlate with acne? Yes.
Do low tryptophan levels correlate with acne? Yes.
Do low ZSOD levels correlate with acne? Yes.
Can this explain why primitive tribes are acne-free? Yes.

This effect of daytime light is simply astounding.
For example, I have long struggled with the ability to consume legumes. I bought into the standard advice that it's a problem of gut flora, if you eat them long enough your gut will adjust and digest them better without gas, etc. If I had a large Coke and a large burrito, the result was 100% predictable: great intestinal discomfort. However, I now know that was simply another problem of failing to suppress daytime melatonin. By living in outdoor light all day, I can slam down a Coke+burrito with zero intestinal discomfort, hardly any gas at all. I've repeated this experiment reliably several times, and outdoor light exposure is like a light switch (heh!) on my ability to digest legumes. I speculate that the growth in acid reflux disease (and the esophageal cancer it can lead to) is probably another result of living in dim light during the day that produces carbohydrate malabsorption.

The unfortunate thing is, although the pill-free cure for my acne is conceptually very simple, it's also very hard for modern people to accomplish. I had to buy a laptop with an extra-bright screen so I could work outdoors during the day -- most people have indoor jobs with no option of working outdoors. Just look at some the many ways we guarantee we won't have a natural melatonin cycle:
Work indoors all day. Indoor light simply does not produce the definitive OFF signal for pineal melatonin that outdoor light does. Even on a severely overcast
day, outdoor light is much more intense (and also simply contains much more of the blue-green frequencies most effective at shutting down melatonin production).
Sleep in the midst of light pollution. Ironically, while bright light is needed to shut melatonin all the way off, very little light is needed to depress the nighttime surge of melatonin that you need to make lots of ZSOD. A night light, a street light shining into your bedroom. Trying to sleep when the sun is up. Flipping on a light when you go to the bathroom. All easy ways to destroy your nocturnal melatonin surge.
Go to bed at different times.
Want to catch that late movie on the weekend? It's just like a form of jetlag -- your body's 24-hour clock just got bumped and may take days to settle back down to match your regular bedtime again.
Take in lots of caffeine. Caffeine will both depress your nocturnal melatonin peak and shorten the hours you sleep, both ways to become melatonin-deprived.
Vegetarianism. Without meat, it becomes more difficult to get enough tryptophan and zinc in the diet. If you combine that with eating high-fructose foods like apples, pears, etc. and living in dim light during the day to produce fructose malabsorption, that greatly raises the odds of acne. This is not to say you can't be a vegetarian and acne-free, but it is plausible that some vegetarians might have to take a couple of pills to get there.
Sunglasses, hats, travel in cars, etc. If you compare modern people to the completely acne-free primitive tribes that still exist, it's almost like we are comically trying to avoid getting any daylight in our eyes. We stay indoors all day. When we travel, we run from shaded building to shaded car (often with dark-tinted windows). We cover our eyes with dark glasses not just when the light is bright, but often just as a fashion statement when the light isn't even bright at
all!
Depression. Depression and a screwed-up melatonin cycle often go hand-in-hand. But of course, acne itself is strongly correlated with depression. This is a real chicken-and-egg scenario. What causes what? The mess is more complicated by the fact that anti-depressants may tinker with the melatonin cycle for better or worse themselves. What is easy to say is that it would be better to not be depressed if you want a normal melatonin cycle (but that may be a complete tautology for some people!).

A Zinc-less Zinc Regimen

I probably can't think of all the inventive ways people destroy their melatonin cycle, but here's the basic remedy to achieve natural levels of melatonin and ZSOD:
Go to bed at the same time each night.
Sleep in total darkness. (Black out your bedroom, go to sleep when the sun goes down, wear a sleep mask, never turn on a light in the middle of the night, etc.).
Avoid caffeine, especially evening caffeine.
Spend all day in outdoor light without sunglasses or hats.
Sleep >= 8 hours. (This becomes easy when you stop megadosing caffeine and suppress your daytime melatonin.)

FAQ
That's too hard. I just can't...
Since I've been doing it for weeks now, I agree with you. I have the luxury of being able to choose to work outside, but it's a pain -- I essentially do office work out on my deck. It's a pain to say I can't go to that midnight movie. It's a pain to put tinfoil on the bedroom windows, wear a sleep mask, etc. It's a pain to open every shade in the house every morning and get my eyes outside ASAP. All I can say is, it's nothing like the pain of cringing when I have to go out in public with acne.
Can't I just take a pill?
Since there are periodic reports in the medical literature of people who hurt themselves by taking extreme doses of zinc (400mg/day, 800mg/day, even more) for their acne, I suspect you can just take a pill, but it could send you to the hospital eventually. I could argue in great detail why you cannot achieve the desired effect by taking melatonin orally, but the fact is many people have tried melatonin pills for acne and they just don't cure it. A melatonin pill before bedtime might help you sleep a little better and jumpstart a busted melatonin cycle, but you really won't need that if you effectively suppress your daytime melatonin. Put another way, if you need that bedtime melatonin pill to sleep, you probably still have a busted melatonin cycle.
Why me? How come my acne-free friends can...
I used to just throw my hands up at this and invoke the fairy dust of "it must be our genes". However, now that I have a detailed theory of the mechanism of acne that seems to me to hold water, I can say that there's a decent chance it's "you" in significant part because you are doing some things different than your friends. For example, in college, were most of my friends staying up until 4am and virtually never going outside like me? Hmmmm, not really. And once you induce carb malabsorption by screwing up your melatonin cycle, then suddenly all the Coke I love to drink does make some difference, and the formerly confusing fact that trying to eat "healthy" by eating fruit really didn't work is incredibly frustrating. The fact is, I suspect I can induce acne in most of the "acne-free" people you know: just keep them in dim light all day every day, keep them in bright light when they're trying to sleep, give them lots of high-fructose foods with every meal (Coke or apples -- your choice), and supply lots of caffeine. There may well be a genetic component to the "why me?" question, but it may be quite small compared the actual details of your acne-inducing lifestyle.
What about dairy?
I still don't know. The fact is, while living the outdoor lifestyle, I have been able to eat a suspicious amount of ice cream without the usually reliable cystic acne response, but I haven't pushed it. It is plausible that the mechanism for dairy producing acne is not beta cellulin, but simply sugar (lactose), and that once carbohydrate malabsorption is cured by suppressing daytime melatonin, dairy isn't a problem. But I do not yet feel certain of that.
Are you acne-free? What pills are you taking?
Every week that I stick with all the rules to maintain my melatonin cycle, I'm acne free. In fact, I sometimes cheat and have caffeine, or miss my bedtime. That sometimes results in a zit, but not always. I stopped taking zinc. I have stopped taking my normal complement of vitamins for a couple of weeks and stayed acne-free, but won't give them up for longer than that because I start getting arthritis.
Maybe it's just Vitamin D?
No. I've been Vitamin D replete for years (>50ng/dl) with no effect on acne. It's possible that if you're horribly Vitamin D deficient (many modern people are) you won't be able to absorb zinc well, compounding your problems. While working outdoors, I work in the shade with no direct sunlight on my skin (though as much view of sky in my eyes as possible). The only times my skin is in direct sunlight is when the sun is low in the sky (little UVB). So, despite spending massive hours outdoors, I haven't tanned at all so far this year. As always, any hope that Vitamin D is really a significant factor in curing acne has to overcome the hurdle of explaining why there's no epidemiological evidence that it varies strongly with latitude (Canadians should have way more acne than Texans if Vitamin D were crucial to the disease).
Can I do [...] instead?
Who knows? But if it's really important to you to get rid of the acne, set aside 2 weeks where you can strictly control your light exposure, and see whether this works. I say "set aside", because I find this regimen amazingly hard. The indoors couch is like a magnet for my butt; I initially had to literally keep a stopwatch outside to keep from fooling myself that I was spending more hours outside than I really was. If you can do it religiously for 2 weeks and it doesn't eliminate all new acne, then the heck with me and my theory. If it does, then you've gained some understanding of how you can control the disease and you can do your own experiments and make your own trade-offs.

Get an hour of outdoor light in the eyes immediately after waking, before work, and before breakfast.
Totally drop caffeine of all forms (it both depletes zinc and of course affects the sleep cycle).
Try to arrange lunch so I can eat outside, and have eyes in outdoor light as many minutes as possible before actually eating the food.
Likewise, try to get eyes into the outdoor light immediately after work and before eating.
Avoid/reduce carbs (especially high-fructose fruits and fizzy drinks) when there was no significant outdoor light exposure before the meal.
Make it a priority to get the all-day outdoor light exposure on weekends.
Carefully tend my sleep cycle to get the best nocturnal surge I can.