Dr. Ron’s Research Review – December 22, 2010

This week’s research review contains information on the DHEA:Cortisol ratio, and the effects of sugar and galantamine.

DHEA:Cortisol Ratio

With aging an imbalance occurs between two adrenal hormones, cortisol and DHEA, that have opposing actions on immune function. (Buford and Willoughby 2008)

A study of 4255 Vietnam-era US army veterans found that DHEAS was negatively associated, and the ratio of cortisol to DHEAS was positively associated with all-cause, cancer and other medical cause mortality. (Phillips, Carroll et al. 2010)

They also found that cortisol, and DHEAS were both related to the metabolic syndrome. Whereas high cortisol concentrations were associated with an increased risk of metabolic syndrome, high DHEAS concentrations appeared protective. By far, the strongest associations with metabolic syndrome were observed for the cortisol:DHEAS ratio; the higher the ratio, the greater the risk of having metabolic syndrome. (Phillips, Carroll et al. 2010)

One study found that sugar alters the level of serum insulin and plasma glucose and the serum cortisol:DHEAS ratio in female migraine sufferers, with migraine participants on average recording a higher sucrose-induced serum insulin level and lower DHEAS level and cortisol:DHEAS ratio.(Kokavec and Crebbin 2010)

A recent study found that CFS patients had lower pre-and post-treatment cortisol levels; higher basal DHEAS values; and higher DHEAS/cortisol molar ratios, which were normalized following four weeks' treatment with 8 mg/d galantamine hydrobromide in the treatment-respondent group. (Turan, Izgi et al. 2009)

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Dr. Ron


Abstracts

Impact of DHEA(S) and cortisol on immune function in aging: a brief review

            (Buford and Willoughby 2008) Download

A decline in the human immune system that occurs with aging is known as immunosenescence. Several factors are involved in the process, including reduced neutrophil function and cytotoxic capacity of natural killer (NK) cells, thymus atrophy and reduced naive T cell number, and lowered B cell antibody production in response to antigen. The endocrine system, specifically the hypothalamus-pituitary-adrenal axis, plays an important role in modulating immune function. With aging an imbalance occurs between two adrenal hormones, cortisol and DHEA, that have opposing actions on immune function. This brief review explores the interactions between cortisol and DHEA and their effects on immune function in aging, as well as potential methods to combat the endocrine-related contribution to immunosenescence, including DHEA supplementation and exercise.

The Effects of Galantamine Hydrobromide Treatment on Dehydroepiandrosterone Sulfate and Cortisol Levels in Patients with Chronic Fatigue Syndrome

            (Turan, Izgi et al. 2009) Download

OBJECTIVE: Mental fatigue, cognitive disorders, and sleep disturbances seen in chronic fatigue syndrome (CFS) may be attributed to cholinergic deficit. A functional deficiency of cholinergic neurotransmission may cause the hypothalamic-pituitary-adrenal axis hypoactivity seen in CFS. Therefore, we investigated the alterations in stress hormones such as cortisol and dehydroepiandrosterone sulfate (DHEAS) in CFS patients before and after 4-week administration of galantamine hydrobromide, a selective acetylcholinesterase inhibitor, and aimed to investigate whether there are any relationships between the probable hormonal changes and cholinergic treatment. METHODS: Basal levels of cortisol and DHEAS were measured in 29 untreated CFS patients who were diagnosed according to Centers for Disease Control (CDC) criteria and in 20 healthy controls. In the patient group, four weeks after 8 mg/d galantamine hydrobromide treatment, cortisol and DHEAS levels were measured again. After the treatment 22 patients who stayed in study were divided into two subgroups as responders and nonresponders according to the reduction in their Newcastle Research Group ME/CFS Score Card (NRG) scores. RESULTS: Important findings of this study are lower pre-and post-treatment cortisol levels and in all CFS patients compared to controls (F=4.129, p=0.049; F=4.803, p=0.035, respectively); higher basal DHEAS values and higher DHEAS/cortisol molar ratios which were normalized following four weeks' treatment with 8 mg/d galantamine hydrobromide in the treatment-respondent group (F=5.382, p=0.029; F=5.722, p=0.025, respectively). CONCLUSION: The findings of the decrease in basal DHEAS levels and DHEAS/cortisol molar ratios normalizing with galantamine treatment may give some support to the cholinergic deficit hypothesis in CFS.

Sugar alters the level of serum insulin and plasma glucose and the serum cortisol:DHEAS ratio in female migraine sufferers

            (Kokavec and Crebbin 2010) Download

Early work has highlighted that a large percentage of migraineurs may have an altered glucidic methabolis due to carbohydrate-induced hyperinsulinism. The aim of this study was to assess the effect of sucrose on biomarkers of energy metabolism and utilization in migraineous females. A total of 16 participants (8=Migraine, 8=Non-migraine) at the mid-point of their menstrual cycle underwent a 15-h fast prior to ingesting 75g sucrose dissolved in 175g water. Blood sampling for the assessment of serum insulin, serum cortisol and serum dehydroepiandrosterone sulfate (DHEAS) and plasma glucose was conducted upon arrival at 09:00h and then at regular 15-min intervals across a 150-min experimental period. The results showed a significant alteration in serum insulin and plasma glucose following sucrose ingestion in the migraine and non-migraine groups. In addition, significant group differences were observed in the level of serum insulin, serum DHEAS, and the cortisol:DHEAS ratio with migraine participants on average recording a higher sucrose-induced serum insulin level and lower DHEAS level and cortisol:DHEAS ratio when group data was compared. It was concluded that while sucrose consumption may potentiate serum insulin in migraineurs this does not result in the development of sucrose-induced hypoglycemia in migraine or non-migraine participants.

Cortisol, DHEA sulphate, their ratio, and all-cause and cause-specific mortality in the Vietnam Experience Study

            (Phillips, Carroll et al. 2010) Download

OBJECTIVES: The aim of the present analyses was to examine the association between cortisol, DHEA sulphate (DHEAS) and the cortisol:DHEAS ratio and mortality. DESIGN: This was a prospective cohort analysis. METHODS: Participants were 4255 Vietnam-era US army veterans. From military service files, telephone interviews and a medical examination, occupational, socio-demographic and health data were collected. Contemporary morning fasted cortisol and DHEAS concentrations were determined. Mortality was tracked over the subsequent 15 years. The outcomes were all-cause, cardiovascular disease, cancer, other medical mortality and external causes of death. Cox proportional hazard models were tested, initially with adjustment for age, and then with adjustment for a range of candidate confounders. RESULTS: In general, cortisol concentrations did not show an association with all-cause or cause-specific mortality. However, in age-adjusted and fully adjusted analyses, DHEAS was negatively related to all-cause, all cancers and other medical mortality; high DHEAS concentrations were protective. The cortisol:DHEAS ratio was also associated with these outcomes in both age-adjusted and fully adjusted models; the higher the ratio, the greater the risk of death. CONCLUSIONS: DHEAS was negatively associated, and the ratio of cortisol to DHEAS was positively associated with all-cause, cancer and other medical cause mortality. Further experimental study is needed to elucidate the mechanisms involved in these relationships.

Cortisol, DHEAS, their ratio and the metabolic syndrome: evidence from the Vietnam Experience Study

            (Phillips, Carroll et al. 2010) Download

OBJECTIVES: The aim of these analyses was to examine the association of cortisol, DHEAS and the cortisol:DHEAS ratio with the metabolic syndrome (MetS) and its components. Design The analyses were cross-sectional. METHODS: Participants were 4255 Vietnam era US army veterans. From military service files, telephone interviews and a medical examination, occupational, socio-demographic and health data were collected. MetS was ascertained from data on body mass index; fasting blood glucose or a diagnosis of diabetes; blood pressure or a diagnosis of hypertension; high-density lipoprotein cholesterol; and triglyceride levels. Contemporary morning fasted cortisol and DHEAS concentrations were determined. The outcomes were MetS and its components. Analysis was by logistic regression, first adjusting for age and then additionally for an array of candidate confounders. RESULTS: Cortisol, although not in the fully adjusted analysis, and DHEAS were both related to MetS. Whereas high cortisol concentrations were associated with an increased risk of MetS, high DHEAS concentrations appeared protective. By far, the strongest associations with MetS were observed for the cortisol:DHEAS ratio; the higher the ratio, the greater the risk of having MetS. The ratio was also significantly related to four of the five MetS components. CONCLUSIONS: The cortisol:DHEAS ratio is positively associated with MetS. Prospective analyses are needed to help untangle direction of causality, but this study suggests that the cortisol:DHEAS ratio is worthy of further study in this and other health contexts.


References

Buford, T. W. and D. S. Willoughby (2008). "Impact of DHEA(S) and cortisol on immune function in aging: a brief review." Appl Physiol Nutr Metab 33(3): 429-33.

Kokavec, A. and S. J. Crebbin (2010). "Sugar alters the level of serum insulin and plasma glucose and the serum cortisol:DHEAS ratio in female migraine sufferers." Appetite.

Phillips, A. C., D. Carroll, et al. (2010). "Cortisol, DHEA sulphate, their ratio, and all-cause and cause-specific mortality in the Vietnam Experience Study." Eur J Endocrinol 163(2): 285-92.

Phillips, A. C., D. Carroll, et al. (2010). "Cortisol, DHEAS, their ratio and the metabolic syndrome: evidence from the Vietnam Experience Study." Eur J Endocrinol 162(5): 919-23.

Turan, T., H. B. Izgi, et al. (2009). "The Effects of Galantamine Hydrobromide Treatment on Dehydroepiandrosterone Sulfate and Cortisol Levels in Patients with Chronic Fatigue Syndrome." Psychiatry Investig 6(3): 204-210.