Relative Hypoglycemia and Neuropsychiatric Symptoms 

I currently have the pleasure of working with a 30-year-old female professional student who was diagnosed with type I bipolar disorder. Her history is long-standing with anxiety reaching back from the age of 5 years old. 

At 20-years old she experienced a major depressive episode during university brought on by the combination of stress during exams and struggling with a toxic relationship. She self-medicated with drugs, alcohol and smoking to the point where her friends, family and doctor were concerned. She often had feelings of suicide and was placed on medications which further exacerbated these symptoms. She switched to cannabis to relieve the anxiety, however this precipitated paranoid-like symptoms, insomnia and asthma. She also started to have panic attacks and complained of physical symptoms including numbness and tingling, leg weakness, tachycardia, and dizziness. This lasted for several years until her depression improved with CBT, exercise, citalopram and the decision to end  her unhealthy relationship. She was struggling with anxiety, depression, and substance abuse when she was referred to me by an addictions coach who was also suspecting insulin resistance.

Her present diet consists of fruit, pastries, juice, ice cream, cheese, chocolate, and very little fat and protein. Despite being quite sensitive to coffee, she would still drink 1-3 cups per day. Her supplements included iron for a history of anemia, and Omega-3 fatty acids. Medications include fluticasone for asthma, pregabalin for sleep, and venlafaxine to manage her depressive symptoms. She is currently in a new long-term relationship, however her partner is not supportive as he continues to make sugary foods, drugs and alcohol accessible in the house.

As requested by the addictions coach, I ordered the Kraft Assay test to determine insulin resistance. The Kraft assay is a specialized 6-point oral glucose tolerance test. Blood is collected via skin prick at fasting, then after consuming a 100g glucose solution, glucose and insulin are measured at ½ hr, 1hr, 2hr, 3hr, 4hr time points (See Figure 1, insulin is not shown). 

The results of the Kraft assay test were intriguing. The results did not match any of the 5 insulin resistance patterns as per Kraft assay criteria. However, she did meet all the criteria for relative hypoglycemia according to Dr. Selzer in a 1966 paper “Relative Hypoglycemia as a cause of Neuropsychiatric Illness”.

The criteria for relative hypoglycemia are: 

  1. At 1/2 hour the blood glucose level exceeds the fasting level by more than 75 mg/dL
  2. The one-hour level is greater than 160 mg/dL
  3. A drop of 10 mg/dL below the fasting level is considered suspicious of relative hypoglycemia and a drop of 20 mg/dL or more is definitive 

Figure 1. A comparison of two 6-point blood glucose charts between my current 35-year old patient and a 52-year old patient from a 1966 study with similar neuropsychiatric symptoms and diet history. Both patients meet the requirements for a diagnosis of relative hypoglycemia, which when placed on a high protein, low carb, caffeine free diet, recovered from their symptoms. The shaded box represents the normal glucose range after consuming a 100g glucose drink. 

In the study, the author describes a patient who has a lot of similarities to my current patient. She is a 52-year-old widow, in 1959 she presented to the doctor with poor concentration, anorexia, apathy, forgetfulness, blurred vision, exhaustion, muscular jerking, panic attacks, and a feeling of numbness of the head. She too had a very similar diet consisting of fruit, toast, ice cream and several cups of coffee throughout the day.

The patient met the criteria for a diagnosis of psychoneurotic depression however the doctor ordered a multi-point glucose tolerance test which revealed a distinct pattern that met all criteria for relative hypoglycemia (see Figure 1). The 52-year-old widow was assigned a high protein, low carbohydrate, caffeine free diet. She had marked physical improvement at six weeks, and at her 4 year follow up, she had no depressive symptoms. This patient relapsed in 1963 but when started back on the diet, she reported significant improvement three months later.  A year following that, she was doing well on the high protein, low carbohydrate, caffeine free diet.

My patient was prescribed a paleo-type diet with no caffeine. Eight weeks later she reported being compliant and was consuming a diet consisting of protein and fat with vegetables. She felt more connected to her body and having a sense of pride and accomplishment. She quit smoking and eliminated dairy. This led to a noticeable decrease in phlegm and asthma symptoms. She continues to abstain from drugs and alcohol with the help of a 12-step program. Her doctor also reports that she is doing much better. She is also very excited to have got accepted in a PhD program. Most importantly, the depressive symptoms have improved dramatically. 

This case reinforces the key points of the 1966 study which is in line with the therapeutic order. Step 1 is to establish the foundations of health. Catching relative hypoglycemia as a cause of neuropsychiatric illness can spare patients years of suffering from the condition itself, complications of self-medicating and invasive treatments. Every patient suspected of neuropsychiatric illness should have a functional multi-point glucose and insulin test to rule this out as a significant driver of their condition. A corrective diet high in protein, low in carbohydrates and free of caffeine, may be the foundation to living a normal life as seen in these two patients with relative hypoglycemia.