DWQA QuestionsCategory: QuestionsCPT II deficiency: weight loss and menstrual cycles
Jo asked 3 years ago

  1. I have a question on weight loss for CPT II patients.

From what I have read, weight gain seems to be mostly related to increased insulin levels, and not so much with calorie restriction and exercise (although they could contribute minimally to weight loss). Insulin suppresses gluconeogenesis (and increases glucose uptake into muscle and fat), however patients with CPT II have limited gluconeogenesis, so would lower insulin levels help with weight loss for CPT II patients as well?
In theory, what would work for CPT II patients to lose weight safely (even without supporting clinical evidence)? Would it help to increase MCT intake? Also, is it possible to also explain the pathophysiology of losing weight for cpt II patients?

  1. Menstrual cycles and CPT II deficiency

This might sound a bit delusional. But there have been a few times where I had difficulty discerning between muscle weakness/the beginning of mild rhabdomyolysis with menstruations. There were 2 episodes where I even had my CK checked because I thought I was at the beginning of rhabdomyolysis, but I was just in my pre-menstrual cycle. I was wondering if menstrual cycles could be related to fatty acid oxidation and if CPT II deficiency could be exacerbated during my menstrual cycle? I found some articles suggesting that estrogen deficiency is associated with increased plasma free fatty acid availability and that estrogen likely has direct, albeit small, effects on adipose tissue lipolysis.
Also, are there any specific recommendations for CPT II patients during menstrual cycles (except from taking hormonal contraceptives to stabilize hormones)? Do the usual recommendations apply (exercising, eating healthy = foods high in magnesium, avoiding refined sugars and caffeine, taking in more calcium)?
Thanks a lot!

INFORM Physician
replied 3 years ago

Jo, I’m going to let Dr. Gillingham, our expert on all things diet and exercise respond to your first question independently. in regards to your second question, you are quite correct that we sometimes see variation in symptoms in our FAO patients related to their menstrual cycle. Some women report an increase in muscle symptoms just before they begin their periods; others are more prone to episodes of rhabdomyolysis either just before or in the early phase of a period. There is indeed evidence that estrogen (which drops just before your period) improves expression of fatty acid oxidation genes and may mediate this phenomenon, but it hasn’t really been studied completely. For patients with significant changes in symptoms during the menstrual cycle, we often prescript a long acting progesterone to suppress the cycle with some success. You should bring your concerns to your treating metabolic physician an discuss your treatment options. I hope this helps. Dr. Vockley

1 Answers
INFORM Scientific Network answered 3 years ago

Thanks for your question on weight loss for CPT II patients. The concept that weight gain is induced by insulin really comes from people who advocate a ketongenic/low carbohydrate approach to weight management. Insulin is an essential hormone; the absence of insulin results in type 1 diabetes. We cannot live without insulin. To attribute weight gain to high insulin levels is oversimplifying a complicated and intricate system that maintains body weight. I do not believe insulin is the real problem with weight gain.

Weight loss is fundamentally burning stored energy sources – either lean muscle mass or fat mass – in the context of negative energy balance. That is hard for someone who has a fatty acid oxidation disorder and fat oxidation is so limited. All patients with CPT2 def have some small amount of residual enzyme activity or some small amount of fat oxidation. The reality is that weight loss has to be very slow and steady over a long period of time with just a slight negative energy balance.

The attached article describes 2 cases studies of weight loss in fatty acid oxidation disorder patients. The goal is to decrease caloric intake slightly and maintain lean body mass with routine exercise and adequate protein intake. Our total energy needs are determined by how much muscle or lean mass we have; the leaner mass, the more energy you burn in a day. So – the goal is to lose weight but primarily fat mass and less muscle mass. We did a study with a higher protein diet including some whey protein and found higher lean mass after 4 months in patients with fatty acid oxidation disorders.

In the case reports, the patients consumed 4-10% MCT. I don’t think more MCT would be helpful but consuming in that range of some MCT was a successful strategy in these cases. For patients with CPT2 deficiency it is also really key to avoid rhabdomyolysis and metabolic crisis. One severe crisis in the hospital with IV glucose and fluids could reverse any prior weight loss because the treatment is to push high levels of glucose and calories.

My recommendation would be to design a diet with a about 500 kcal per day restriction combined with routine exercise to maintain muscle mass. Consume a small amount of MCT and adequate protein throughout the day. The goal is slow steady weight loss. I recognize this is very hard, and requires a lot of patience. I think you also have to be forgiving and loving to yourself as you proceed. Many people without a fatty acid oxidation disorder cannot lose weight. CPT2 deficiency makes weight loss even more challenging. My best to you, Dr. Melanie Gillingham.