Most nutritionists believe that low blood sugar three or four hours after eating is a frequent cause of irritability, anxiety, fatigue, heart palpitations, shakiness, headaches, hunger or mental fogginess. They call this syndrome "hypoglycemia."

Most mainstream physicians, however, don't believe hypoglycemia is a genuine condition. They cite research showing that most people who develop a hypoglycemic-type reaction actually have fairly normal blood sugar levels at the time of their symptoms.

There is an explanation for this paradox. Hypoglycemia is real, but low blood sugar is not its immediate cause. Hypoglycemic symptoms such as fatigue and irritability result from an overabundance of the hormones adrenaline and cortisol (a close cousin of cortisone). Thus, a more apt explanation of hypoglycemia may be too much adrenaline and cortisol rather than too little blood sugar.

The evidence for this explanation appeared in the Journal of the American Medical Association more than 13 years ago. Sadly, few physicians make reference to this important research or even know of its existence.

Scientists from the University of Maryland, Johns Hopkins University and the National Institutes of Health identified 19 people who had typical hypoglycemic symptoms several hours after eating. They gave each person a high-sugar meal as part of a glucose tolerance test. However, unlike previous researchers who measured subjects' blood sugar every hour or half hour, they measured blood sugar second-by-second through a catheter placed in a vein.

The difference between continuous and hourly blood sugar was crucial. Hypoglycemic symptoms developed in these 19 subjects almost exactly at the point when their blood sugar was lowest--several hours after eating. Pinpointing it to this exact moment led researchers to the adrenaline/cortisol connection. Previous studies that relied on hourly blood sugar measurements were more likely to miss this point on the blood sugar curve, and hence, miss the hormone connection.

It is more than coincidence that when blood-sugar was lowest, hypoglycemic symptoms began, since the bottom of the sugar curve is also the moment that the body's antistress hormones (adrenaline and cortisol) change drastically. Most likely, it is these hormonal events and the chain reactions they generate that comprise the actual cause of hypoglycemic symptoms.

The High-Sugar Response We can understand these physiological events by examining the normal response to a high-sugar meal. People without hypoglycemic symptoms show a quick rise in blood glucose soon after eating sugar. In response, the pancreas releases insulin to drive blood sugar down. Normally, insulin continues to decrease blood sugar three or four hours after eating--until it falls below the fasting level but is still within an adequate range. Precisely at this lowest point of the blood sugar curve, the adrenal glands release a small jolt of adrenaline. Adrenaline increases blood sugar, raising it back to pretest baseline levels without resulting in undesirable symptoms.

The subjects with hypoglycemic symptoms showed a similar pattern, but with major differences. Their blood sugar levels fell lower after three or four hours, to an average lowest blood-sugar level of 57 mg per deciliter vs. 72 mg per deciliter for the controls. This distinction is statistically, but not always clinically, significant.

The real disparity was the dramatic change in the 19 test subjects' adrenaline and cortisol levels. Adrenaline blood levels at the bottom of the glucose curve surged by more than 1,200 percent--quadruple the increase seen among controls. Surging adrenaline has the effect of drinking three cups of coffee, stimulates the body in many ways, and can produce all the various symptoms of a hypoglycemic reaction. Hypoglycemics also produced a marked increase in cortisol, while the normal subjects did not. Cortisol, which raises blood sugar, may also result in depression, fatigue, anxiety and loss of muscle tone.

Why are hypoglycemics vulnerable to this hormonal explosion? And why does it occur precisely at the bottom of the blood- glucose curve? The most reasonable explanation is that adrenaline and cortisol are the body's way of preventing falling blood-sugar levels from dropping through the floor. Sugar is the brain's main source of fuel, and very low blood sugar, such as 30 mg per deciliter, can cause irreversible brain damage.

The bottom line is that the agitating side effects caused by adrenaline and cortisol are the price hypoglycemics pay to prevent a too-low blood-sugar level.

But why do hypoglycemics require such heroic hormonal labors to keep blood sugar in line? We don't really know the answer, but genetics, nutrition, and physical and emotional stresses probably contribute. Animal studies show that blood-sugar instability increases when stress occurs. It's also known that stress increases hypoglycemic symptoms among humans. Hypoglycemics who moderate their lifestyles and practice stress-management skills can often take more liberties with their diet without paying a price.

Although this study updates our understanding of how eating sugar induces hypoglycemic symptoms, the basic dietary recommendation remains similar to that described by Carlton Fredericks and other nutrition pioneers--eat frequent meals of moderate size that are low in sugar and reasonably high in protein. Strictly limit caffeine and alcohol. Combined with stress management, lifestyle moderation and a survey for unrecognized illness, this regimen delivers the best long-term results.

Richard Podell, M.D., is clinical professor of family medicine at the UMDNJ-Robert Wood Johnson Medical School in New Brunswick, N.J. He is the author of Patient Power: How to Protect Yourself Against Medical Error (Fireside, 1996).

REFERENCES

Chalew, S., McLaughlin, J., & Mersey, J. "The use of the plasma epinephrine response in the diagnosis of idiopathic postprandial syndrome," JAMA, 251: 612-15, Feb. 3, 1984.