Is Low Cholesterol Dangerous?

Low cholesterol is responsible for diminished production of steroid hormones and resultant poor health in a 29-year-old woman.

Americans are increasingly concerned about cholesterol. But is cholesterol a harmful substance that should be avoided at any cost? Is the evidence so clear?

It is very well established that high cholesterol is strongly associated with cardiovascular disease. It is equally well established, however, that low cholesterol, or hypocholesterolemia, is also a predictor of acute and chronic illnesses as well as mortality. Unfortunately, the public is largely unaware of this. While we are bombarded with advertisements for cholesterol-lowering drugs, we also need to be aware of possible problems related to low cholesterol.

A number of investigators have reported on the relationship between chronically low cholesterol levels (usually less than 160 mg/dL) and excess risk for most cancers, hemorrhagic stroke, suicide, affective disorders (depression, bipolar disorder, and schizophrenia), and certain gastrointestinal conditions.1-5 Remarkably, several studies have found that patients with low cholesterol levels had the highest rates of death from coronary heart disease.6,7

Cholesterol is the substrate from which is derived the cascade of all steroid hormones. Examination of patients with affective disorders, seizure disorders, anxiety, autism aggression, attention-deficit hyperactivity disorder, obsessive-compulsive disorder, and physically oriented acute and chronic illnesses must focus on the study of disturbed cholesterol metabolism. From our point of view, hypocholesterolemia is the perfect marker for an underlying health condition and a serious risk factor for associated diseases.

Here we present the case report of a patient with low cholesterol.

Background
During an initial visit, a 29-year-old Caucasian woman presented with severe fatigue, no energy, depression, anxiety, panic attacks, no libido, poor sex drive, very poor short-term memory, excessive body weight, an irregular menstrual cycle since her teenage years, premenstrual syndrome, sleeping problems, nearly permanent herpes on her lips, and dermatitis around the mouth.

The patient reported having a bowel movement every other day, and sometimes every third day. She also claimed to be unable to control her emotions, and said she had had most of these symptoms since her early twenties.

The patient reported normally lunching on pizza, ice cream, and junk food. Despite her desire to lose weight, she said did not exercise because she had no energy to do so. She had no desire to try any dietary or exercise program, and only wanted medicine for weight loss.

Her medical history was significant for persistent menstrual disorder, obesity, and depression. The patient took Zoloft® for depression without any significant effect. She denied using tobacco or “heavy” alcohol consumption. A physical exam confirmed that the patient was vastly overweight. Vital signs were as follows: height, 5’6”; weight, 242 pounds; body-fat percentage, 58% (normal range is 17-24%); blood pressure, 120/80 mm Hg; pulse, 76 beats per minute; respiration, 18 breaths per minute.

Diagnosis and Treatment
We suspected that many clinical features of this case—such as depression, severe fatigue, menstrual and sexual disorders, sleeping problems, and extremely poor short-term memory—could be related to neuroendocrine perturbations.

Initial laboratory assessment revealed a low level of total cholesterol: 130 mg/dL. We also found that her production of basic steroid hormones was significantly diminished.

Hormonal levels were as follows (normal range are shown in parentheses):

• DHEA-S 87 (65-380 ug/dL)
• Pregnenolone 30 (10-230 ng/dL)
• Total estrogen 87 (61-437 pg/mL)
• Progesterone 0.4 (0.2-28 ng/mL)
• Total testosterone 33 (14-76 ng/dL)

It was very difficult to evaluate the patient’s hormone disorder, as she had a very irregular menstrual cycle. Sometimes she had menses in two weeks, sometimes in three or four months.

The initial treatment program focused on correcting a hormonal disorder related to low cholesterol. We explained to the patient that we would not initiate a weight-loss program until we had restored her “foundation,” a process that would take approximately three to four months.

The patient began taking 100 mg of DHEA and 100 mg of pregnenolone each morning. She was instructed to take 0.25 ml of a progesterone gel (50 mg/ml) daily during the first 10 days after completing menses, then 0.4 ml daily until menses and 0.15 ml daily during menses. Additional supplements suggested were 1000 IU of vitamin E taken in the morning, 1000 mg of vitamin C at bedtime, and one capsule of MetaRest (containing 3 mg of melatonin, 250 mg of kava root extract, and 10 mg of vitamin B6) at bedtime. We also recommended exercise lasting 15 minutes twice a day.

After one week, the patient stopped taking Zoloft®. Her depression, anxiety, and panic attacks disappeared. After one month of treatment, we suggested a one-month parasite-cleansing program (Paraway® Pack), as the patient had two dogs and many of her symptoms have been associated with parasites. After the cleansing program, multiple digestive enzymes were added to her regimen for one month. After two months, a 28-day menstrual cycle was restored. Her sleep had improved significantly, her libido and sex drive had increased remarkably, and her bowel movements were normalized. The dermatitis around her mouth had disappeared, as had the herpes on her lips. Even in the absence of a weight-loss program, the patient lost 18 pounds in the first three months. She increased her exercise regimen to walking two miles three times a week and running two miles three times a week.

After three months on this program, we reduced the patient’s daily dose of DHEA to 50 mg per day, then added the following additional supplements for weight loss: 4 g of conjugated linoleic acid (CLA) in the morning before breakfast; two capsules of chitosan before lunch and two capsules before dinner; one capsule (1000 mg) of hydroxy-citric acid (HCA) three times daily with meals; one capsule (200 mcg) of chromium picolinate three times daily; and one scoop of soy protein daily before exercise. We recommended eating small meals 3-4 times daily, eliminating all junk food, and eating the last meal of the day before 6 p.m. During the first two weeks of additional treatment, we suggested drinking 400 ml of whole buttermilk every evening in place of dinner.

After 15 months, the patient stopped using progesterone gel, we cut her dose of DHEA to 25 mg, and she continued to exercise and eat a balanced diet. She had lost 62 pounds, reducing her weight to 180. After decreasing her dose of DHEA, the patient again began experiencing mild depression, and in one month, she regained nearly 12 pounds. We recommended that she increase her DHEA dose to 50 mg, as well as take 50 mg of zinc at bedtime and 1000 mg of cat’s claw daily. Her complaints disappeared and she increased her exercise regimen, running five miles daily.

After two and one-half years on this program, the patient’s weight had fallen to 146-148 pounds and stabilized. Her body-fat percentage had been reduced to 18%. During this time, the patient attended college and graduated with a high grade point average. She no longer complained about memory problems.

Blood tests (drawn during the second week of her menstrual cycle) showed a significant improvement in hormonal profile:

• DHEA-S 360 (65-380 ug/dL)
• Pregnenolone 157 (10-230 ng/dL)
• Total estrogen 454 (61-437 pg/mL)
• Progesterone 1.8 (0.2-28 ng/mL)
• Total testosterone 61 (14-76 ng/dL)

It is important to stress that during the weight-loss period, the patient cannot continue to gradually lose weight. After losing 20-30 pounds, it is necessary to have a maintenance or stabilization period of two to three months during which the patient stays in the same weight range. We repeated the parasite cleansing program every four months. The patient proved very sensitive to changes in doses of DHEA and pregnenolone, with pregnenolone fluctuating between 50 and 200 mg and DHEA between 25 and 100 mg. Once her menstrual cycle had consistently stabilized, the patient no longer needed to take progesterone.

Today, the patient continues to exercise and eat a balanced diet, and still supplements with vitamins C and E, pregnenolone, and DHEA.

Commentary
High cholesterol may be associated with decreased production of critically important hormones.8,9 We believe that elevated cholesterol is a consequence of insufficient hormone production and serves as compensatory mechanism. Conversely, low cholesterol is responsible for poor production of steroid hormones. We believe that in studies in which cholesterol levels below 160 mg/dL were correlated with potentially dangerous outcomes and diseases—such as suicide, alcoholism, disorders of the lung and digestive system, cerebral hemorrhaging, stroke, and some cancers—patients had limited amounts of raw material (cholesterol) for hormonal production and reconstruction of cellular membranes.

After reviewing the medical literature on the link between hypocholesterolemia and various pathologies, we suspected that this patient’s problem was insufficient hormone production. Lack of cholesterol for steroidogenesis can be a causal factor for the multiple disorders mentioned previously. One study showed impaired reproductive efficiency in hypo-cholesterolemia induced animals.10 In this case report, we can hypothesize that hypocholesterolemia played a crucial role in the patient’s deficient production of steroid hormones, and that her multiple symptoms were related to those deficiencies. From our point of view, any program that does not restore “foundational chemicals” (such as steroid hormones) is doomed to failure. This is because metabolism will continue to be slow, intestinal absorption will be poor, the immune system will be defective, and the neurohormonal system will be imbalanced. This is why we always stress the importance and necessity of the first step of any program: restoration of optimal levels of steroid hormones.

Cholesterol is especially abundant in the nervous system and plays an important role in cellular structure and function. Changes in serum levels may affect neurotransmission in the central nervous system. Substantial evidence suggests that serum cholesterol levels may be associated with variations in mental state or personality.11 Imbalanced blood chemistry and lipid metabolism can usually influence depressive states. It is known that neurosteroids such as DHEA may antagonize cortisol activity and have mood-elevating effects of their own.12 A low DHEA level can be an indicator of diminished capacity to protect against stress.

Intensive pharmacological studies suggest that neurosteroids may be involved in learning and memory processes.13 Patients with fatigue may experience significant impairments in learning and memory,14 and can suffer from major depression, anxiety, and panic disorder.15 Treatment for chronic fatigue is usually symptom based and includes pharmacological and behavioral strategies.16 Our findings suggest that physiological and psychological factors work together. Restoring normal physiology is central to correcting disorders such as those described in this case report.

Obesity’s causes are poorly understood, and both the prevention and treatment of obesity are difficult.17 In this case, a weight-loss program was initiated only after a significant improvement in quality of life. It is known that:

• HCA may be helpful in weight loss because of its effects on metabolism.18

• CLA can reduce fat deposi- tion and increase lipolysis in adipocytes, possibly with enhanced fatty-acid oxidation in both muscle cells and adipocytes.19

Hypocholesterolemia is usually associated with reduced antioxidant reserves and absolute vitamin E levels.20 This is why our program incorporated antioxidants.

Exercise was also an important part of our program, as physical activity can enhance the synthesis and release of cholesterol in the liver.21 This is very important because an enhanced cholesterol level can be expected to increase hormonal production, thus reducing the amount of hormones to be replaced.

This case study describes a patient who had low level of steroid hormones related to low cholesterol, with multiple symptoms typical of hormonal deficiencies. Multimodal approaches using hormones, nutritional supplements, exercise, and lifestyle modifications can help control most problems related to low cholesterol. Hypocholesterolemia can be a potential warning sign of concurrent diseases or a signal of rapidly declining health.

Sergey A. Dzugan, MD, PhD, was formerly chief of cardiovascular surgery at the Donetsk Regional Medical Center in Donetsk, Ukraine. Dr. Dzugan’s current primary interests are anti-aging, biological therapy for cancer, cholesterol, and hormonal disorders.