Monday, May 21, 2012


Sudden infant death syndrome (SIDS) is defined as the sudden, unexplained, usually nocturnal, death of an infant between the ages of about 2 months to roughly the end of the first year. The peak incidence is three to four months, unusual after six months and rare after one year. It is more common in male infants. Gross examination at autopsy is invariably negative, but there is plenty of evidence in the medical literature that there are microscopic changes in the brainstem. These changes have been explained as “agonal”, meaning that it is damage produced at the time of death rather than related to the cause. There is every reason to believe that these microscopic changes provide important clues that will be discussed later in this discussion. SIDS has been under investigation for many years and nobody has come up with a definite explanation for the tragedy. The latest information that has proved to be greatly beneficial is that the prone position in the crib is more dangerous than the supine. It has been suggested that the prone position is more likely to lead to suffocation or possibly that the infant might inhale chemicals in the mattress that are placed there commercially as a fire retardant. Anyway, this has led to a statistically significant reduction in this terrible event that has marred the lives of so many parents. There is still an incidence of SIDS that is unexplained and it seems to be more in the lower socioeconomic segment of the population where diet may be more inappropriate for good health. Many years ago I became deeply interested in the vitally important metabolic activity of vitamin B1 (thiamine). This came about because I was confronted with a 6-year old boy who had a neurological disease that occurred intermittently. It was invariably initiated by some form of stress such as a vaccination, a mild head injury, a sudden change in ambient temperature, or an infection. It took several years to solve the problem and required the help of a researcher at the National Institutes of Health. It proved to be thiamine dependency. This produces the same effects as thiamine dietary deficiency but there was a genetically determined defect in a crucially important thiamine requiring enzyme that enables glucose to be used as fuel for all body cells and particularly the brain. I have written repeatedly that the brain requires huge amounts of energy so it was not surprising that this boy’s illness affected the normal function of his brain. What was even more important was that this effect centered more on the lower, more primitive, part of the brain. This part of the brain contains all the vital mechanisms that enable us to compute an adaptive response to the constant changes that we meet daily in our environment. The intermittent nature of the disease indicated that the energy supply could cope with a smooth daily lifestyle but was inadequate to meet an adaptive response to some form of physical or mental stress. This boy could be protected from his brain illnesses by taking huge doses of thiamine daily. If he had a simple infection such as a cold, he would have to double this dose. It taught me how a stress event such as a relatively mild to moderate head injury, or even a simple infection such as a cold, can be converted to serious brain illness in a person with marginal energy metabolism. (Lonsdale D, Faulkner W R, Price J W, and Smeby R R. Intermittent cerebellar ataxia associated with hyperpyruvic acidemia, hyperalaninemia, and hyperalaninuria. Pediatrics 1969;43:1025-34). Because of this, I began an exhaustive library search for everything that I could find about thiamine metabolism. Not surprisingly, it led me to the complex symptoms caused by the ancient scourge known as beriberi, now known by all physicians to be due to a combination of thiamine deficiency and empty calories, most often in the form of white rice. It is clearly a disease that is related to the rate of metabolism, so infantile beriberi is more lethal than in childhood and the adult form is more chronic, representing the rate of metabolism as we become older. I found that infantile beriberi causes sudden death and in the early days of research of this disease one of the investigators had made an important statement. He said that “anywhere that public health statistics report sudden infant death, the unequivocal diagnosis is beriberi. There is no other disease known that affects infants like this”. I discovered a paper written in 1944 by a British medical officer of health. She had been sent from Britain to Hong Kong, then a British protectorate, to study a form of sudden infancy death in Chinese women who were breast feeding these infants. (Fehily L . Human milk intoxication due to B1 avitaminosis. Brit Med J 1944;2:590-2). She had discovered that the cause of this death was infantile beriberi caused by thiamine deficiency in the mothers’ breast milk. Some readers may remember that the Japanese invaded China before World War II and the Chinese women were kept on a starvation diet of rice. There was severe malnutrition in both mothers and infants but, curiously enough, the sudden infancy deaths disappeared. When the Japanese invaders were driven out of Hong Kong, these mothers had restoration of ad lib rice in their diet. Just as curiously, the sudden infant deaths began to reappear. This may have been the first inkling in humans that the ratio of carbohydrate calories to thiamine was the important issue. We now know that the intake of “empty carbohydrate calories” overloads the capacity of thiamine to process it. Sir Rudolph Peters, in Cambridge, England, had clearly shown this to be true in his experiments with thiamine deficient pigeon brain cells in 1936. The production of carbon dioxide from thiamine deficient cells was no different than that exhibited by thiamine sufficient cells UNTIL GLUCOSE WAS ADDED. The thiamine sufficient cells immediately began respiration (CO2 production) while the thiamine deficient cells remained inert. Peters called this the "catatorulin effect". Fehily had noted in her paper that this infantile beriberi had the exact epidemiology as “cot deaths”, the term used for SIDS in Britain, and that it might be worth some research. It was initially thought that there was no way of predicting a SIDS incident but it was found that certain symptoms were potentially predictable, the most important one being short episodes of sleep apnea (cessation of breathing) occurring in sleep. My colleagues and I turned our attention to this and found that a study known as Brainstem Auditory Evoked Potential (BAEP) could actually predict SIDS potential risk in infants with any of the symptoms brought to our attention by parents. (Lonsdale D, Nodar R H, and Orlowski J P. The effects of thiamine on abnormal brainstem auditory evoked potentials. Cleve Clin Quart 1979;46:83-8). We also found that we could successfully treat affected infants with large doses of thiamine, given by injection. Another investigator, Joan Cardell, had found evidence that magnesium deficiency could be blamed and it is now well known that magnesium and thiamine are intimately related in their metabolic functions. I visited a researcher in Australia who had found that some abnormality in thiamine metabolism was indeed related to SIDS. Curiously, he had found that the level of thiamne in blood from SIDS victims was abnormally high. A pediatric colleague in New Zealand had found an unusual incidence of SIDS in his locality and sent me the results of blood thiamine values from 20 anonymous patients that had died. Among them were four SIDS. I was asked to let him know if I could spot the SIDS by the higher value of the blood thiamine. Three were obvious and the fourth was marginally higher and it was easy to spot the four. We concluded that it was a form of thiamine dependency similar to that in the child described above and with perhaps a different mechanism that still has not been explored. Thiamine deficiency (or dependency) in that part of the brain is equivalent to deprivation of oxygen, hence the so-called “agonal” defects in the brainstem of SIDS infants is evidence of cause rather than effect. All of this has largely been ignored by pediatricians and those investigators researching the problem of SIDS. The brilliant work of Peters is probably known by few, for medical journals consider that a scientific reference older than about 10 years is “out of date”. This is in spite of the fact that all scientific knowledge is built on the shoulders of those who have gone before and have often made fundamentally important observations that are major clues. I decided that I would place this information for public view, since it surely must have general interest, particularly to the would-be mothers who have read about SIDS and often nurse a secret dread of the possibility if and when they become pregnant. It should remind them that diet during that pregnancy is of fundamental importance in the healthy future of the baby.


  1. ( note this important website for preventive measures

  2. These preventive measures are well authenticated but SIDS still occurs nevertheless. There is no doubt that a biochemical change in the brainstem, induced either genetically or from malnutrition in pregnancy, is a cause in some cases.