Zyprexa/olanzapine and weight gain and B12 metabolism associated problems

I took olanzapine 2 and a half years ago and have since then acquired various medical problems.
After being traumatized one too many times without apologies and reinforced and sent to live and think out of my lizard brain like ptsd I just couldn’t bounce back the same nor forgive as easily anymore
Old meds stopped working for me and since traumas I’ve wasted my life getting back to my healthy comfortable size after each medication which usually depressed me and kept me from living a more comfortable fulfilling life… but it’s like I’d get stabbed in the back again and instead of getting an apology or life restored I’d end up going on meds and wasting a few years recovering to get stable and drama again and meds and weight loss and… anyway. Zyprexa seemed to work for my mood, but I felt like sleeping too much and my legs felt irritable and I had perpanerol for that, but I felt weak all the time and dizzy and like I couldn’t even hold my niece for long. I enjoyed previously my health and the way it worked for me and how it managed weight naturally and appreciated being mobile with energy at least. I found it unfair that besides losing much of my life and new start that that previous hard work at recovery for mentally and physically was thrown away with trauma and on medication. I gained 6 pounds a week. I tried preparing for it this time because of the previous times of my health and hard work getting thrown away this time, but working out twice a day didn’t stop it and so I feared eating and before I just blamed myself and the environment since I wasn’t in my usual healthy element. Nooo it was the worst weight gain by far and I could feel my skin stretching and it didn’t feel like a normal healthy weight gain either and before I at least retained a shape and a waist, but thus just came on with higher fat proportions and maybe visceral fat who knows? My perfect labs started to get effected and my years of eating healthy trying to avoid the diabetes in my family and from my little skinny grandma. Did I say on this genetic site that they keep updating I have a varying health score of A+ for weight, D-F for schizophrenia, A+ for personality I guess bc of empathy and a downgraded F for diabetes and better score for cholesterol levels. A for depression… haha, not if you get schizophrenia. I’ve become apathetic after trauma and backstabbing but it returns but it gets harder and I have to make sure my needs are met. It tells me how I might be effected on drugs and says I don’t respond well to anti depressants, I do well on Zyprexa, but there’s more risk of weight gain. My sugar cholesterol had been better before, sugar was low and now… changing. I told my new doc about the weight gain and how uncomfortable I was but they said stay with it. Should I ask a pregnant doctor if they care about my weight gain that’s troubled me in the past from meds… they were nice but I wander why the they didn’t stop it earlier as the later doctor said. A doctor finally told me the truth in a different city. In that city they both seemed to address these issues more and wandered why the others did not. I’ve only been uncomfortable since then for the past two years and not living normally while establish a safer more secure supportive environment yet distant to protect my well being while not fulfilling and it makes me think I forgot what heakthlimess and mindfulness felt like. They said weight loss is very hard. They told me the truth and said it was notorious for weight gain. They would not fix it but it was kind of a slap in the face to be offered nutritious advice classes or portion control by those who never took this when weight was manaeageble before meds and healthy eating. They switched my meds and I’ve been taking classes now that I can think a bit better and live a bit less out of my lizard brain that sociopaths put me into so I think it really is triggered by environment if you have a genetic disposition. Classes sometimes cover a more fulfilling life and how environment plays a role and they’re honest about complete reliability on drugs. I might take pharmacology, but I’m afraid it’ll depress me.
I suddenly started getting shocks to the right side of my face recently where I was hit by a truck six years ago and it spread to the whole right side and gets more intense with swallowing or air or being awake… or the weather so my dr said maybe B12 or folic acid (B9) which go hand in hand. The next dr she referred me to said my B12 level was 3,000 almost and fine but to me that was off the charts and I don’t know if it was the gel test and not metabolized and it does okay a role in helping to turn fat into energy to use so I asked for a retest and folic acid test to name sure it’s not a deficiency or metabolism problem with B12 or folic acid. How do you fix that? My TSH is 1.89 out of 5, which is good but it’s one of many metabolisms. I read some online stories that B12 metabolism is a common issue with patients on olanzapine. They said it’d take time to get out of my system and I’m grateful for my stomach finally growling but I’m so tired and exercising is not as enjoyable or easy and humiliating and less able at this weight. Doing things are so different and harder now and I wear out easier and I feel pity for all with these problems bc you basically suffer 24/7 if you’re expected to live like this with the excess. Schizophrenia is hard but… sigh. So much judgement and ppl assuming you’re lazy and it’s lack of education in nutrition. I made an A+… and still don’t get it and please… females are programmed to get obsessed with being thin and eating disorders so… why assume it’s portion control? Anyway… I read a study I’ll post how some ppl say you could gain weight up to two years after stopping Zyprexa and another study that is studying short term meds to try to lessen the fat increase.


In mice and in humans, treatment with the second generation antipsychotic drug olanzapine (OLZ) produces excessive weight gain, adiposity and secondary metabolic complications, including loss of glucose and insulin homeostasis. In mice consuming a high fat (HF) diet, a similar phenotype develops, which is inhibited by the analgesic acetaminophen (APAP) and by the antioxidant tetrahydroindenoindole (THII). Therefore, we examined the ability of APAP and THII to prevent metabolic changes in mice receiving OLZ.

Design and Measurement

C57BL/6J mice received either a normal diet or a high fat diet, and were administered OLZ (3 mg/kg body weight/d), alone or with APAP (35 mg/kg body weight/d) or THII (4.5 mg/kg body weight), for 10 weeks. Parameters of body composition and metabolism, including glucose and insulin homeostasis and oxidative stress, were examined.


OLZ treatment doubled the HF diet-induced increases in body weight and percent body fat. These increases were partially prevented by both APAP and THII, although food consumption was constant in all groups. The THII protection was associated with an increase in whole body and mitochondrial respiration. OLZ also exacerbated, and both APAP and THII prevented, HF diet-induced loss of glucose tolerance and insulin resistance. Since increased body fat promotes insulin resistance by a pathway involving oxidative stress, we evaluated production of reactive oxygen and lipid peroxidation in white adipose tissue (WAT). HF diet caused an increase in lipid peroxidation, NADPH-dependent O2 uptake and H2O2 production, which were further exacerbated by OLZ. APAP, THII, and the NADPH oxidase inhibitor, diphenyleneiodonium chloride (DPI) each abolished oxidative stress in WAT.


We conclude that both APAP and THII intervene in the development of obesity and metabolic complications associated with OLZ treatment.

Keywords: Acetaminophen, Diet, Mice, Obesity, Olanzapine, Oxidative stress
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  1. Introduction
    Obesity poses a growing global health threat, due in large part to the consumption of diets high in fat content, coupled with sedentary lifestyles (1). Another risk factor for gain in body weight and adiposity are the use of drugs for treatment of psychotic disorders. These atypical (second-generation) antipsychotic drugs, such as olanzapine (OLZ; Zyprexa™; 2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5]-benzodiazepine) are used to treat millions of people suffering from psychotic episodes. While highly effective for their intended use, a high percentage of patients exhibit unfortunate secondary complications associated with the excess weight and obesity, including cardiovascular disease, dyslipidemia, and the development of insulin resistance and type 2 diabetes mellitus (T2DM), cardiovascular disease and stroke (2–4). It is therefore not surprising that a recent study found that persons with schizophrenia lose about 25 years of potential life due to premature cardiovascular mortality (5).

Standard anti-diabetic drugs such as metformin and thiazolidinediones (e.g., rosiglitazone, piaglitazone), or off-label drugs such as the anti-epileptic topiramate (Topamax™), are often prescribed with OLZ to prevent the development of metabolic complications, especially hyperglycemia (6). However, these prescription medications are expensive and have their own adverse side effects that tend to limit their use.

Mice are similar to humans by increasing body weight and adiposity when consuming a high fat diet (HF diet), and thus mouse models have proven useful for the study of metabolic disorders associated with a HF diet (7;8). In mice, acetaminophen (APAP; 20 mg/kg body weight/day) ameliorated the HF diet-induced gain in body weight and fat mass, and the associated metabolic complications (9;10). Histological examination of tissues that exhibit toxicity with high-dose APAP treatment (liver, kidney, olfactory epithelium) showed no evidence of toxicity under our dosing regimen (9). Similar to APAP, tetrahydroindenoindole (THII; 4b,5,9b,10-tetrahydroindeno[1,2-b]indole), prevented metabolic complications associated with excess weight and obesity that result from a HF diet (11). Therefore, we evaluated the potential for APAP and THII to protect against metabolic toxicity induced by OLZ in mice. APAP and/or THII may offer inexpensive alternatives or adjuvant therapy with drugs commonly used to treat metabolic disorders.

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2. Materials and Methods
2.1. Chemicals

OLZ was obtained from Thermo Fisher Scientific (Pittsburgh, PA). THII was synthesized as described and was 98% pure as determined by NMR and GC/MS (12). All other chemicals and reagents were from Sigma-Aldrich Chemical Company (St. Louis, MO) as the highest available grades.

2.2. Animals and treatment


How Zyprexa Alters Your Metabolism
Zyprexa, is an incredibly popular psychiatric medication manufactured by Eli Lilly. Yet, although Zyprexa was originally developed for the treatment of schizophrenia and bipolar disorder, it has now gained widespread use for the treatment of depression as well.

Back in 2007, Lilly was required to add a strong warning label to Zyprexa indicating the drugs tendency to cause weight gain, high blood pressure, and other metabolic problems. It was found that weight gain could continue for as long as two years after the medication was stopped and that one in six patients who took the medication would gain more than 33 pounds after two years of using it. And this is information that was added to the label.

These issues, weight gain and changes in metabolism, profoundly threaten long-term health. The relationship with respect to the drug is clear, but what hasn’t been well defined is the actual mechanism by which Zyprexa causes these events to occur.

A new study brings to our attention some very important new science as relates to this mechanism. The research, hearing in the journal, Translational Psychiatry, evaluated the effects of Zyprexa (generic name olanzapine) on the gut bacteria of laboratory animals. The animals received Zyprexa for 21 days given by injection into the abdominal cavity.

Dramatic changes were seen in the array of gut bacteria in animals who received Zyprexa and these changes were associated with significant weight gain, Inflammation, and fat deposition.

When the experimental animals also were given specific antibiotics that kept certain bacterial species from growing, these metabolic changes did not occur as aggressively when the Zyprexa was administered. The authors concluded:

These results suggest that the gut microbiome has a role in the cycle of metabolic dysfunction associated with olanzapine, and could represent a novel therapeutic target for preventing antipsychotic-induced metabolic disease.
I present this information to again drive home the point that so much of what occurs to change human metabolism in a dysfunctional way leading to things like diabetes, weight gain, autoimmunity, and inflammation, has its genesis in the gut bacteria. Changes in the gut bacteria can take place not only based upon our food choices, but as a consequence of various pharmaceutical drugs that are so commonly prescribed. This takes the notion of “above all do no harm” to a new level as, in moving forward, we need to consider how drugs alter the highly influential gut microbiome.