Wednesday, July 15, 2009

Benefits and Risks of Zinc Supplementation in Eating Disorders, ADHD, and Depression

Zinc supplementation may help treat anorexia nervosa, ADHD, and treatment-resistant depression.

Zinc is a metallic element involved in multiple aspects of human cellular function, metabolism, growth, and immune function. It is required for the function of about 100 human enzymes. The human body contains about 2000-3000 mg of zinc, of which about 2-3 mg are lost daily through kidneys, bowel, and sweat glands. The biologic half-life of zinc in the body is about 9 months, so it can take months or years for changes in dietary habits to substantially change zinc status, unless the intake is very high for short periods.

Red meat is a particularly rich source of zinc. Vegetarians may have a harder time getting an adequate amount from the diet. The prevalence of zinc deficiency may be as high as 40% worldwide.

When referring to zinc dosage, it is best to refer to "elemental zinc". Different types of zinc preparations (e.g. zinc gluconate or zinc sulphate) have different amounts of elemental zinc. For example, 100 mg of zinc gluconate contains about 14 mg of elemental zinc. 110 mg of zinc sulphate contains about 25 mg of elemental zinc.

Here are references to articles written by a Vancouver eating disorders specialist between 1994 and 2006, advising supplementation of 14 mg elemental zinc daily (corresponding to 100 mg zinc gluconate daily) for 2 months in all anorexic patients:

Here's a 1987 article from a pediatrics journal, showing improvement in depression and anxiety following 50 mg/d elemental zinc supplementation in anorexic adolescents:

In this 1990 open study, anorexic patients were treated with 45-90 mg elemental zinc daily, most of whom had significant improvement in their eating disorder symptoms over 2 years of follow-up.

Here's a 1992 case report of substantial improvement in severe anorexia following zinc supplementation:

Zinc depletion may lead to an abnormal sense of taste (hypogeusia or dysgeusia). This sensory abnormality improves with zinc supplementation. Here's a reference:

Here's a randomized , controlled 2009 Turkish study showing that 10 weeks of 15 mg/day zinc supplementation led to improvement in ADHD symptoms in children. However, a close look at the study shows a bizarre lack of statistical analysis comparing the supplemented group directly with the placebo group. When you look at the data from the article, both groups improved to a modest degree on most measures, with perhaps a little bit more improvement in the zinc group. The analysis here was insufficient, I'm surprised a journal would accept this.

Here's a 2004 reference to a study showing that 6 weeks of 15 mg elemental zinc daily as an adjunct to stimulant therapy improved ADHD symptoms in children, compared to stimulant therapy plus placebo. In this case, there was a valid statistical analysis:

Here's a 2009 study showing that zinc supplementation improves the response to antidepressants in treatment-resistant depression. The dose they used was 25 mg elemental zinc daily, over 12 weeks.

Here's an excellent 2008 review article about zinc deficiency, and about the potential role of zinc supplementation in a wide variety of diseases (e.g. infections ranging from the common cold, to TB, to warts; arthritis; diarrhea; mouth ulcers). The review shows that zinc may have benefit for some of these conditions, but the evidence is a bit inconsistent:

Here is a warning about zinc toxicity: {hematological toxicity from taking 50-300 mg zinc daily for 6-7 months. The toxicity was thought to be due to zinc-induced copper malabsorption leading to sideroblastic anemia}

Here is a nice website from NIH summarizing the role of zinc in the diet, in the body, some of the research about health effects, and about toxicity. It sticks to a recommended daily intake of 10-15 mg elemental zinc for adults, or about 5 mg for young children. It states that the maximum tolerable daily intake levels are about 5-10 mg for young children, 20-30 mg for adolescents, and 40 mg daily for adults:

Here is a reference to another excellent review of zinc requirements, benefits, and risks. It makes more cautious recommendations about zinc supplementation, advising no more than 20 mg/day of zinc intake in adults. In order to prevent copper deficiency, it also advises that that the ratio between zinc intake and copper intake does not exceed 10.

So, were I to make a recommendation about a zinc supplementation trial, I would advise sticking to amounts under 20 mg (elemental) per day for adults, and to ensure that you are getting 2 mg of copper per day with that.


Anonymous said...

I have often wondered and thought about the rewarding effects of self induced starvation. Now I am purely basing this off of subjective experience and limited observations of biased populations but I believe that people who may not find eating a rewarding experience may choose to go long periods without food, so that when they do eat there is a greater feeling of reward. Sometimes I think that perhaps people who have low endogenous dopamine levels use such tactics to boost the rewarding effects of certain activities in order to feel what others would consider typical enjoyment??

Just a thought.

Alhough I can't get access to the entire article.

GK said...

Thank for the reference, it is interesting to consider the neurobiological aspects of eating disorders.

There are probably many neural sources of reward for various behaviours, both in the immediate and longer-term time frames. I suspect the feeling of immediate hunger itself may become attached to reward circuitry, in a similar mechanism as self-injury or addiction. Also, there can be a cognitive overlay, employing other parts of the brain to add to the sense of reward, as the feeling of hunger leads to a possibly satisfying perception of control, altered body image, or hard work that is getting accomplished.

While there may be some neurochemical sources of relief for these dynamics (such as medications; and most certainly of optimized nutrition), I believe the core resolution of these varieties of problems is through behavioural and cognitive retraining: to employ the brain's plasticity to let the starvation-pleasure connection fade, while training neural circuits associating healthy eating with satisfaction and pleasure. I believe such training can then end the vicious cycles of self-destructiveness which eating disorders bring. The work of training most likely would need to be very intense, a degree of magnitude similar to that of stroke rehabilitation or training for the olympics. On a positive note, such a herculean challenge may appeal to those who have previously applied such intensity to driving their self-destructive habits. Strict, lengthily prolonged abstinence from the disordered behaviour and all its adjuncts would be necessary, while also working hard at challenging the obsessional patterns of negative thinking which would otherwise tempt one to give up, or to go back to the old patterns.