N-acetyl-L-cysteine: use with hope, use with caution

N-acetyl-L-cysteine is an up and coming supplement, which is gaining popularity among body builders. What's interesting is that it's also showing promise as a natural antidepressant.

It makes sense that it would work for both, since NAC is an antioxidant. In the case of exercise, it helps to repair the damage created in the process of metabolizing energy to fuel the exercise. When it comes to depression, it helps to slow down the oxidative process that has been destroying neurons.

Other potential mental health issues it is showing promise for include: bipolar disorder, schizophrenia, and obsessive-compulsive disorder. It may also help with polycystic ovary syndrome, another issue I specialize in treating.

NAC is to be treated with respect, however. In mice, in large doses it has been found to increase blood pressure in the lungs and right ventricle of the heart, creating symptoms similar to what is seen in animals subjected to an oxygen-deprived environment for 3 weeks.

While this supplement may have some very useful potential, it is important to work with a professional who knows how to dose it in order to maximize your benefit from it without putting yourself at risk. The guy at the corner bodybuilding store, who makes more money, the more you use, is likely not this person. A registered dietitian with specific training ins sports nutrition is your better bet.

Ferreira FF, Biojone C, Joca SR, Guimarães FS. Antidepressant-like effects of N-acetyl-L-cysteine in rats. Behav Pharmacol. 2008 Oct;19(7):747-50

Biochemical and brain differences in bipolar disorder--that nutrition might be able to help

These guys think like me. Instead of coming up with a pill that fixes what appears to be wrong on the outside...why not start on the inside and figure out what's really causing the problem?

This group of researchers started out looking at tissue samples of people who had had depression. What they discovered was that these individuals had low levels of docosahexaenoic acid (DHA, if you read this blog you know that's fish oil and marine algae) in their red blood cells and their cortices. The cortex is the part of the brain that does logical, rational problem solving.

They decided to poke around some brains that had been under the influence of bipolar disorder in their time and discovered that there were several abnormalities. As with depressin, DHA levels were low. Arachidonic acid and stearic acid levels were also low. Brains of individuals who had been on mood stabilizing or antipsychotic medications were not as deficient. The deficiencies appeared to be more severe if alcohol abuse had been an issue.

It's not clear whether or not the issue is totally dietary, or if there is some kind of abnormal metabolic process that alters fatty acid ratios, but it does seem that researchers in this area are leaning toward the possibility that nutrition is extremely important to brain function--as well as to the management of psychiatric disorders.

It causes me to wonder why dietary controls are not a standard protocol in psychotropic drug studies, but that's a topic for another blog post. I'm sure you'll see that soon!

McNamara RK, Jandacek R, Rider T, Tso P, Stanford KE, Hahn CG, Richtand NM. Deficits in docosahexaenoic acid and associated elevations in the metabolism of arachidonic acid and saturated fatty acids in the postmortem orbitofrontal cortex of patients with bipolar disorder. Psychiatry Res. 2008 Sep 30;160(3):285-99. Epub 2008 Aug 20.

Oh! Why the graphic? Just some random thinking...all this writing about fish, and brains, and fish for brain health kind of has me wondering...if fish might not be more intelligent than we give them credit for, if fish ever get depressed...and if there is such a thing as a manic salmon?

"Going up in smoke: tobacco smoking is associated with worse treatment outcomes in mania."

Bipolar disorder, to me, is a fascinating disorder. It seems to affect some very intelligent and creative people, and that, I believe, is precisely why it is so hard to treat. The manic episodes it can produce can be part of the thrill of having the disorder. I've had more than one client who accepted medical treatment for bipolar disorder complain that the medication took away the "edge". People started to ask if anything was wrong. We kind of like manic people for their charisma, for the creative performances, work output, etc., that they give us. And, because mania is a natural kind of high, giving it up can be somewhat of a chemical straight jacket.

However, bipolar disorder is also neurodegenerative. Meaning if it progresses unchecked, all that extra brain energy that's requiring oxidation of glucose to fuel all those charismatic neurons is also creating a process that's not unlike a "rusting out" of the brain. So, if we want to preserve the creativity and contributions of people born with this kind of hardwiring, we have to work harder to understand the hardwiring, and develop medications that don't leave people feeling zombied. Plus, we have to encourage lifestyle choices that promote longevity.

One of the worst risk factors, it appears, (in other words, a group of people we now know we have to work extra hard to learn how to help), is people with bipolar disorder who smoke. In this study, what was found was that the subjects who smoked did not respond as well to the medications they were given.

What is really interesting about this study, is that the medications tested happened to be antipsychotics that have been found to be helpful in some cases of bipolar disorder. No traditional mood stabilizers, such as lithium, were used. I wish that had been included in this study, because this study may not be saying that bipolar smokers have worse treatment outcomes, as much as it says when a patient is diagnosed with bipolar disorder who smokes, they may do better with a different category of medication.

Our patients depend on us to be diligent with scientific process and not let our bias interfere with their well-being.

Berk M, Ng F, Wang WV, Tohen M, Lubman DI, Vieta E, Dodd S. Going up in smoke: tobacco smoking is associated with worse treatment outcomes in mania. J Affect Disord. 2008 Sep;110(1-2):126-34. Epub 2008 Feb 15.

Why are cats and bipolar disorder showing up in the same blog post?

I volunteer for two different animal rescue groups here in Phoenix. I like to say that when things get tough with humans, I de-stress with the animals. As my friends in these organizations have realized what I do for a living, I've been presented with some interesting opportunities to combine both interests. You may have seen the post about Norm, the abandoned cat who we eventually lost due to consequences of prolonged and severe malnutrition. Thanks to my nutrition colleagues, I was steered toward a refeeding protocol developed by the World Health Organization used with children in third world countries. It's had limited and successful use in animals. I have submitted it to our vet staff for review, with the hopes that the next time an animal in need comes our way, we won't have to go through the emotional stress of losing it.

Last week, my friend Gerda paid me to consult with her about her cat Yani. I know Yani from the Arizona Animal Welfare League, and Gerda is a PhD candidate at Arizona State University. She is so diligent, she has plotted Yani's weight on a white board and kept his intake records over several months so we can problem solve. (Being the animal lover that she is, she put "anonymous" rather than "Yani" next to his assigned color so he wouldn't develop body image issues over being identified as obese!) So all of the medical and nutritional history I have for him makes this like a dream project in a fancy nutritional lab.

Despite Gerda's best efforts and documentation that Yani's food intake is limited, he continues to gain weight. He is, in turn, exhibiting signs and symptoms of depression. No interest in exercise. Extreme interest in food. Interest in food with any kind of environmental stimulation. I find this fascinating, because I used to work in eating disorders. Humans with eating disorders tend to connect all of their eating issues to some kind of psychological issue--an abuse, a trauma, an emotional issue. But here we have a cat, exhibiting the same behaviors and as far as we know he's not been verbally belittled, he's not had his body image assaulted by reading a few too many issues of Elle or Vogue, and he's certainly not being coerced by food ads on television. (Fortunately for Yani, and my Ivy League-ingrained insistence on maintaining proper scientific method, Gerda is more of a PBS than a Desperate Housewives person.)

So we've started a Facebook group and we're trying to figure out why Yani is getting fat when, thanks to a conscientious kitty mom and dad, he is following all the rules.

It seems, we've learned, that cats don't do well with carbohydrates. Many cat foods have carbohydrate fillers. And in reading cat food labels, I've seen supposedly high-protein foods that are high protein because they contain fillers such as corn gluten and soy protein that any self-respecting cat would never choose on his own. Cats are meat eaters. We've switched Yani primarily to meat, tossed the fillers, and we're experimenting with carnitine, a supplement that has been found to help metabolize fat and has actually been studied in cats.

I am particularly interested in what happens with Yani, because it's been my experience that people with mood disorders also seem to have problems with their weight. Some of it is binge eating, I know, but there just seems to be something metabolic that goes with a mood disorder that causes a proneness to gaining weight. It can even often be seen in the body type--solid center of gravity, proneness to gaining weight around the abdomen, skinny legs, in women, a tendency toward bustiness--it's the most common body type I treat in working with mental illness. I just described the apple shaped body type that is defined as a risk factor for metabolic syndrome, if you're not familiar with it. More and more, my observation is being supported in the literature, that people who have metabolic syndrome tend to have this body type...and to be more prone to mood disorders. This long drawn out dissertation is my attempt to be politically correct at saying that sometimes there is a genetic tendency toward a mood disorder, and that can be strongly linked with problems with weight.

When you see the issue manifest in a cat, who isn't subject to the same kind of emotional conditioning as a human, it really points to the fact that some people are, weight and calorie wise, completely different from others.

Researchers recently looked at the medical records of 161 individuals with bipolar disorder. Over three fourths of them were were overweight, and almost half were obese. High triglycerides, high blood pressure, and diabetes were noted at a rate greater than is observed in the general population. Over half met the criteria for metabolic syndrome.

There was a trend toward even greater incidence among individuals whose bipolar disorder was being managed with second generation antipsychotics (for example, Zyprexa). However, the trend existed whether or not those medications were part of the scenario.

My point? There are many psych meds that get blamed for weight gain. The reality is that they may exacerbate a pre-existing tendency toward weight gain, but they do not cause it. That genetic profile may benefit from a certain kind of diet. Just as Yani cannot blame his weight gain on poor social conditioning and must be encouraged to follow a lifestyle that minimizes his identified genetically-based medical risks, so must people with bipolar and other mood disorders. Weight gain is not necessarily an excuse to not take medications. A well-planned diet may help to minimize weight gain, and that is why it can be helpful to work with a nutritionist specializing in mental health, in conjunction with a psychiatrist who understands the complex interactions of mood, weight, and hormone function.

Fiedorowicz JG, Palagummi NM, Forman-Hoffman VL, Miller del D, Haynes WG. Elevated prevalence of obesity, metabolic syndrome, and cardiovascular risk factors in bipolar disorder. Ann Clin Psychiatry. 2008 Jul-Sep;20(3):131-7.

Special note: In order to continue to protect Yani's identity and self-image, the photo above is merely a stock photo of a random cat. The photo is included solely for illustrative purposes and is not intended to belittle or poke fun at any animal whose weight exceeds kitty culturally-accepted norms.

Topamax and kidneys...these two will probably never be BFF's

I've noticed in looking at my blog statistics that a previous entry on kidney stones resulting from topiramate (Topamax) use continues to be one of my most visited pages on this blog. So when I found more information about this medication and its effect on kidneys I wanted to be sure to share it.

Within 5 days of starting topiramate, the six subjects in this study experienced an average drop of calcium in their urine of about 31% and of citrate by about 40%. When calcium and citrate are not showing up in the urine, it's likely because it's accumulating elsewhere. Like in kidney stones.

Interestingly, increasing the topiramate dose seemed to improve calcium readings and to worsen citrate readings. Meaning you might get less of one kind of kidney stone and more of another.

The authors of this study said that the degree of reduction of urinary citrate was profound enough to be compared to the clinical presentation of renal tubular acidosis. This is a condition in which the body's pH is shifted to an unhealthy level, promoting important changes such as bone demineralization. And THIS will cause rickets in children and osteomalacia in adults. These are not things you will see or feel in those first few days. You need to measure them clinically.

I would strongly recommend, if you and your physician have concluded that the absolute only way to manage your bipolar disorder, your migraine, or your epilepsy, is with topiramate, that you closely monitor your urinary metabolites to be sure you're not doing more harm than good.

And if you're one of those souls who's been convinced that it might be nice to try topiramate to see if it helps you lose weight, consider that you might not just be
losing fat, you might also be losing bone. What's the point of being thin if you have to be sick when you get there?

The only way to know is to monitor. Please don't stick your head in the sand and hope it's not happening to you.

Warner BW, LaGrange CA, Tucker T, Bensalem-Owen M, Pais VM Jr. Induction of progressive profound hypocitraturia with increasing doses of topiramate. Urology. 2008 Jul;72(1):29-32; discussion 32-3.



I found a photo of a kidney stone on the 'net. Imagine trying how it feels to pass something this big through an opening about as big as a piece of cooked pasta. Now you know why I'm trying to get your attention!

Zinc supplementation during lithium therapy

One of the most important things to understand about psychiatric disorders, is that they induce metabolic stress on the brain that can be significant enough to induce degeneration. An important treatment goal for any psychiatric disorder is to pursue balance and deter this process as much as possible.

Sometimes, as is the case with lithium, the treatment can be as deleterious as the disorder. In the process of stabilizing mood, lithium can also reduce the activity of several antioxidant enzymes. Antioxidants are chemicals that delay and prevent degeneration and aging. These enzymes promote chemical reactions that help to preserve brain tissue.

One very powerful tool that can slow down this process, is nutrition. Researchers in India were able to demonstrate that zinc supplementation given to rats who were also being given lithium, helped to restore antioxidant enzyme activity.

Zinc is required for many reactions occurring in the brain and nervous system so I'm not surprised at this. I also would venture to guess that other antioxidants would have been helpful as well. The message is not to load up on zinc, but to be sure that if you have bipolar disorder, that your nutritional choices include a wide variety of foods from all food groups. I'm always surprised at how little nutrition information is given to people for their psychiatric diagnoses. It's a powerful little strategy that can go such a long way!

Bhalla P, Chadha VD, Dhar R, Dhawan DK. Neuroprotective effects of zinc on antioxidant defense system in lithium treated rat brain. Indian J Exp Biol. 2007 Nov;45(11):954-8.