Hospitalized bipolar patients, suffering rapid mood swings from depressive states to manic states, have been found to have significantly higher levels of diabetes mellitus - almost three times the national average. Consequently, according to a report in a recent issue of the American Journal of Psychiatry, there may be a link between the two diseases.1 Earlier in the 20th century, this would not have been a surprise,2 for then elevated blood sugar was seen to be a sign of abnormal mental states.3

But by the mid-century, people had become infatuated with psychoanalysis, which shot down physical explanations. Freudian interpretations became the dominant paradigm, and the possibility that biochemistry could help us understand depression (or other mind syndromes) was shelved. Now, once again, dysfunctions, diseases, and syndromes of the body are the subjects of investigation as possible causal agents in psychosis and depression.


Hospitalized bipolar patients, 
suffering rapid mood swings from depressive 
to manic states, have significantly higher levels of 
diabetes mellitus - almost three times 
the national average.

Dr. Frederick Cassidy and colleagues at Duke University Medical Center in Durham, North Carolina, examined 345 patients who had bipolar disorder (age range from 20 to 74). Of these patients, 9.9% also had diagnosed diabetes mellitus, compared to a frequency of 3.4% found in the same age group throughout the general United States population. Diabetes mellitus, or diabetes for short, encompasses both Type 1 diabetes (juvenile-onset, or insulin-dependent) and Type 2 diabetes (adult-onset, or non-insulin-dependent).

According to Dr. Cassidy, "Possible explanations for this comorbidity [diseases coexisting] include a genetic relationship between the two diseases, a causal relationship in which the development of diabetes mellitus or mania increases the risk of the development of the other disorder, or a functionally overlapping disturbance present in both diseases."4 Moreover, he speculates that the typical medication used for bipolar disorder might further increase the risk of the development of diabetes, either directly or because weight gain is a side effect, and obesity increases the incidence of diabetes. Thus, it would appear that bipolar patients are in jeopardy of a "double downswing," one of which is depression and the other, diabetes.


Lower DHEA levels were correlated 
with elevated blood glucose.

DHEA MAY IMPROVE DIABETES AND MOOD
Dualities abound in nature, so it is not surprising that there are identified nutrients and hormones that benefit both individuals with blood-sugar irregularities (possibly including diabetics) and those with the symptoms of garden-variety depression (possibly including bipolar depressives).

Low levels of certain steroid hormones have been associated with diabetes for nearly 30 years. In this regard, DHEA (dehydroepiandrosterone) has been reported to ameliorate diabetes in rats.5 When researchers investigated the relationships among blood glucose, serum DHEA, age, and weight in 169 healthy men (mean age 46.5 years), they found that, as so many other studies had already shown, DHEA levels declined with age.6 While there was no significant corresponding relationship between age and weight (as measured by body mass index), lower DHEA levels were correlated with elevated blood glucose. It is thought that lower DHEA levels may contribute to the rise in blood glucose that occurs with aging.


Nearly 50% of patients taking up to 90 mg/day 
of DHEA experienced at least 50% improvement 
in depressive symptoms over the course of the 
study, with specific improvements in energy, 
stamina, libido, and sense of well-being.

In another study, DHEA supplementation was found to increase the ability of insulin to induce glucose uptake in two strains of diabetic rats.7 As we age, insulin tends to become less effective in metabolizing glucose, so it may be plausible to deduce that DHEA supplementation can play a role in improving glucose utilization.

DHEA: A BETTER ANTIDEPRESSANT
Another principal benefit of DHEA is its ability to enhance one's sense of well-being. In a recently reported, double-blind, placebo-controlled trial, DHEA was able to provide significant antidepressant benefits for some patients suffering from major depression. Nearly 50% of patients taking up to 90 mg/day of DHEA experienced at least 50% improvement in depressive symptoms over the course of the study, with specific improvements in energy, stamina, libido, and sense of well-being.8

5-HTP FOR DIABETES AND MOOD 
Since diabetes is associated with low brain serotonin levels (which are associated with depression and other problems), as well as overeating and carbohydrate craving, diabetics typically have problems with their weight, tending to become obese. In a double-blind, placebo-controlled study, 25 overweight, non-insulin-dependent diabetics were given orally 750 mg of 5-HTP per day for two weeks, or a placebo. Those receiving 5-HTP (5-hydroxytryptophan, the precursor to serotonin) decreased their carbohydrate intake and lost weight.9 No dietary restriction was prescribed. Twenty of the 25 subjects (nine from the 5-HTP group and 11 from the placebo group) completed the study. The data confirmed serotonin's role in reducing caloric intake - principally through reduced carbohydrate consumption - and suggested that 5-HTP is a safe way to improve dietary compliance for non-insulin-dependent diabetics.


In a recent study, DHEA was able to provide 
significant antidepressant benefits for some 
patients suffering from major depression.

There have been scores of studies showing the ability of 5-HTP to enhance mood. The basis for the use of 5-HTP (as a serotonin precursor) is the hypothesis that a cerebral serotonin deficiency can play a role in the origin of depressions. In such situations, 5-HTP has flowered, proving even to have a prophylactic effect.10 Good moods are maintained with 5-HTP, just as bad ones are relieved.

PHENYLALANINE MAY HELP WITH DIABETES AS IT ELEVATES MOOD 
Twenty-three patients with diabetes with fatty infiltration of the liver, and 27 patients without it, had their amino acid levels examined.11 Compared to the 27 controls, all the diabetics were found to have a reduction in their levels of phenylalanine (a precursor to noradrenaline). Untreated diabetics tend to lose their responsiveness to noradrenaline, which has been found to play an important role in thermogenesis, the burning of fat.12This renders diabetics vulnerable to obesity. Synthesizing increased amounts of noradrenaline - or preventing its reuptake - can help to maintain adequate thermogenesis even in diabetics. In one study of a noradrenaline reuptake inhibitor, obese patients with non-insulin-dependent diabetes or hypertension lost significantly more fat than subjects on placebo.13


Those receiving 5-HTP decreased their 
carbohydrate intake and lost weight.

One of the best-known roles of phenylalanine is as a precursor to the neurotransmitter noradrenaline (your brain's version of adrenaline), which plays an important role in brain processes for fast memory recall, reaction time, mental energy, alertness, attention, and goal-seeking.14 With low levels of noradrenaline, mood can decline, making it hard to be fulfilled or content, let alone happy. This is why the practice of using antidepressant reuptake inhibitors has now been expanded to include noradrenaline as well as serotonin.15

GET ON THE UPSWING
Nutritional supplements containing the above nutrients - DHEA, 5-HTP, and phenylalanine - plus other cofactors and ingredients intended to enhance health and improve memory function can help replenish some of the body's stores of precious molecules, including DHEA, serotonin (from 5-HTP), and noradrenaline (from phenylalanine), which tend to decline with age and are collectively associated with the double downswing of blood-sugar irregularities and garden-variety (mild) depression. Get back on your feet, firmly into a productive and fulfilling life.

References

  1. Cassidy F, Ahearn E, Carroll J. Elevated frequency of diabetes mellitus in hospitalized manic-depressive patients. Am J Psychiatry 1999;156:1417-20.
  2. Kooy FH. Hyperglycaemia in mental disorders. Brain 1919; 42:214?89.
  3. McCowan PK, Quastel JH. Blood-sugar studies in abnormal mental states. J Ment Sci 1931; 77:525-48.
  4. Diabetes common in hospitalized bipolar patients. Reuters Health Sep 22 1999. http://www.reutershealth.com/frame_archive.html
  5. Maksimov SV, Demchenko SV. Concentration of 17-ketosteroids (17-KS) and their fractions in the urine of males of different age with diabetes mellitus. Probl Endokrinol (Mosk) 1970 Nov-Dec;16(6):21-7.
  6. Thomas N, Morris HA, Scopacasa F, Wishart JM, Need AG. Relationships between age, dehydro-epiandrosterone sulphate and plasma glucose in healthy men. Age Ageing 1999 Mar;28(2):217-20.
  7. Ishizuka T, Kajita K, Miura A, Ishizawa M, Kanoh Y, Itaya S, Kimura M, Muto N, Mune T, Morita H, Yasuda K. DHEA improves glucose uptake via activations of protein kinase C and phosphatidylinositol 3-kinase. Am J Physiol 1999 Jan;276(1 Pt 1):E196-204.
  8. Wolkowitz OM, Reus VI, Keebler A, Nelson N, Friedland M, Brizendine L, Roberts E. Double-blind treatment of major depression with dehydroepiandrosterone. Am J Psychiatry 1999 Apr;156(4):646-9.
  9. Cangiano C, Laviano A, Del Ben M, Preziosa I, Angelico F, Cascino A, Rossi-Fanelli F. Effects of oral 5-hydroxy-tryptophan on energy intake and macronutrient selection in non-insulin dependent diabetic patients. Int J Obes Relat Metab Disord 1998 Jul;22(7):648-54.
  10. van Praag HM. Serotonin precursors in the treatment of depression. Adv Biochem Psychopharmacol 1982;34:259-86.
  11. Zlatkina AR, Sidel'nikova MV, Borodulina OV, Dubova VG. Characteristics of the amino acid spectrum of blood serum in diabetes mellitus. Probl Endokrinol (Mosk) 1977 May-Jun;23(3):7-12.
  12. Shibata H, Perusse F, Bukowiecki LJ. The role of insulin in nonshivering thermogenesis. Can J Physiol Pharmacol 1987 Feb;65(2):152-8.
  13. McNeely W, Goa KL. Sibutramine. A review of its contribution to the management of obesity. Drugs 1998 Dec;56(6):1093-124.
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  15. Mongeau R, Blier P, de Montigny C. The serotonergic and noradrenergic systems of the hippocampus: their interactions and the effects of antidepressant treatments. Brain Res Brain Res Rev 1997 Apr;23(3):145-95.