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aging in men is associated with decreases in bone mineral density (BMD) (18, 19), lean body and muscle mass

strength (22, 23) and aerobic capacity (24), as well as with increases in total and abdominal body fat, low-density lipoprotein cholesterol, and/or low-density lipoprotein/high-density lipoprotein cholesterol ratios (25, 26, 27, 28), all of which also occur in nonelderly hypogonadal men

Most (1, 5, 6, 7, 8, 9), but not all (10, 11, 12), cross-sectional studies have demonstrated a decrease, with age, in total T in men

total T, but not free T index, tended to decrease with greater BMI is consistent with prior studies showing that obesity is associated with decreases in both SHBG and total T, with an unchanged T-to-SHBG ratio

The conventional definition for T levels is statistical (values more than 2 sd below the mean), rather than functional. Such a definition does not reflect clinical realities, such as the existence of characteristic individual set points for circulating hormone levels, below which one, but not another, individual may develop metabolic changes of hormone deficiency; nor does it address the concept of reserve capacity, the possibility that persons with hormone levels 2 sd below the population mean still may have adequate hormone concentrations to meet their metabolic needs.

both T and free T index (a calculated value related to free or bioavailable T) decreased progressively at a rate that did not vary significantly with age, from the third to the ninth decades.

contrasts with other studies showing diminished free, as well as total, T in with increasing total (48) or abdominal (49) obesity in men.

Our analysis of date-adjusted T and free T index levels, by decade, showed that relatively high numbers of older men in this generally healthy population had at least one hypogonadal value (defined as below the 2.5th percentile for young men)

The issue of how properly to define hypogonadism, or indeed any hormone deficiency, remains problematic

The decrease in free T index was somewhat steeper than that of total T, owing to a trend for an increase in SHBG with age

LH for gonadal function

It would clearly be better to define the lower limit of normal for a hormone as: the blood level at which metabolic and/or clinical sequelae of hormone deficiency begin to appear, or the level below which definite benefits can be demonstrated for hormone supplementation for a significant proportion of the population

an effect of aging to lower both total and bioavailable circulating T levels at a relatively constant rate, independent of obesity, illness, medications, cigarette smoking, or alcohol intake

The GKI can be useful in determining the success of dietary therapies that shift glucose- and lactate-based metabolism to ketone-based metabolism

Alzheimer’s disease, Parkinson’s disease, traumatic brain injury, chronic inflammatory disease, and epilepsy

The zone of metabolic management is likely entered with GKI values between 1 and 2 for humans

Optimal management is predicted for values approaching 1.0, and blood glucose and ketone values should be measured 2–3 hours postprandial, twice a day if possible

Preclinical studies have demonstrated a clear linkage between GKI and therapeutic efficacy

the Warburg effect (aerobic fermentation of glucose) is a common metabolic malady expressed in nearly all neoplastic cells of these and other malignant tumors

Aerobic fermentation (Warburg effect) is necessary to compensate for the insufficiency of mitochondrial oxidative phosphorylation in the cells of most tumors

Normal brain cells gradually transition from the metabolism of glucose to the metabolism of ketone bodies (primarily β-hydroxybutyrate and acetoacetate) for energy when circulating glucose levels become limiting

Ketone bodies bypass the glycolytic pathway in the cytoplasm and are metabolized directly to acetyl CoA in the mitochondria

Tumor cells are less capable than normal cells in metabolizing ketone bodies for energy due to their mitochondrial defects

daily activities and emotional stress can cause blood glucose levels to vary making it difficult for some people to enter the predicted zone of metabolic management

a clear association of the GKI to the therapeutic action of calorie restriction against distal invasion, proliferation, and angiogenesis in the VM-M3 model of glioblastoma

The results suggest that GKI levels that approach 1.0 are therapeutic for managing brain tumor growth

Therapeutic efficacy of the KD or calorie restriction is greater with lower GKI values than with higher values

One advantage of FMI, as compared to the BMI concept, is that it amplifies the relative effect of aging on body fat

We believe that the definition of obesity based on relative body fat (ie percentage) remains of great value for the definition of obesity. However, in a situation in which a patient is losing weight without substantially changing his/her relative body fat (as is the case with crash diets), the calculation of FMI will quantitatively reveal the amount of body fat store lost.

high sensitivity of FMI (respectively FFMI) to a slight change of body fat stores

Sarcopenic obesity has been defined as a low FFM associated with a high body fat

relative FFM lower than 73% (ie a relative body fat greater than 27%) in men and a FFM lower than 62% (ie a body fat greater than 38%) in women.

FMIs greater than 8.2 kg/m2 in men and 11.8 kg/m2 in women would define the 'overfat' status (rather than the overweight range) in terms of fat mass

In young women, FMI averaged 5.5 kg/m2 (range 5th-95th percentile: 3.5-8.7 kg/m2) ie 38% higher than in males

the average FMI for young men was 4.0 kg/m2