A Comprehensive Guide to Preventive Blood TestingMay 2004
By Penny Baron
Vitamin B12 and folate
Folic acid helps protect against chromosomal (genetic) damage; prevents atherosclerosis caused by excess homocysteine; in high doses has been shown to decrease risk of cardiovascular disease; is needed for the utilization of sugar and amino acids; may prevent some types of cancer; promotes healthier skin; and helps protect against intestinal parasites and food poisoning. It has also been established that folic acid can prevent spina bifida; therefore, women of childbearing age should increase their RDA of folic acid.
Vitamin B12 and folate deficiencies are most commonly due to problems of malabsorption (B12: gastrointestinal disorders, pancreatitis, tapeworm, and alcoholism; folate: drug interference and jejeunal mucosal disease) or inadequate dietary intake (B12 in rare cases of strict vegetarian diets and folate in general malnutrition or alcoholism).
Low levels of B12 are also seen in patients with multiple myeloma and iron deficiency, in those who smoke, and the elderly; in patients with cancer, aplastic anemia, and folate deficiency; in patients on hemodialysis; and in those who ingest high doses of vitamin C.
High levels may be increased in acute and myelogenous leukemia, polycythemia vera, leukocytosis, and liver disease.
Folic acid levels may be decreased in alcoholics; those with a chronic disease, undergoing hemodialysis, or having anorexia nervosa; and in premature infants and the elderly. Besides pregnancy, increased doses of folic acid may be indicated in hyperthyroidism, neoplasia, hemolytic anemias, and psoriasis.
Low levels of DHT may be associated with decreased sex drive, erectile dysfunction, male pseudohermaphroditism, or pseudovaginal perineoscrotal hypospadias. Increased levels of DHT may be implicated in male-pattern baldness (alopecia), hirsutism (excessive hair growth in women), benign prostatic hyperplasia, and acne.
If DHT levels are elevated, drugs such as Avodart®, Proscar®, or Propecia® may be considered.
Fasting insulin and HOMAIR
Insulin resistance (when the body does not respond to the insulin that it produces) is a common finding in metabolic disorders, including glucose intolerance, dyslipidemia, hyperuricemia, and hypertension,62 and is associated with an increased risk of symptomatic coronary artery disease.63 Furthermore, approximately 25% of persons with insulin resistance will go on to develop type II diabetes.
According to Bonora et al, the prevalence of insulin resistance estimated by HOMA is 66% in patients with impaired glucose tolerance, 84% in NIDDM (non-insulin-dependent diabetes mellitus) subjects, 54% in persons with hypercholesterolemia, 84% in hypertriglyceridemia patients, 88% in patients with low HDL cholesterol, 63% in patients with hyperuricemia, and 58% in hypertensive patients. In patients with a combination of glucose intolerance, dyslipidemia and/or hypertension, the prevalence of insulin resistance was 95%.62
Data also show that HOMA-estimated insulin resistance is an independent predictor of cardiovascular disease in patients with type II diabetes.64
Insulin resistance may also be an indictor and likely cause of kidney disease in persons with type I diabetes, according to a study at the University of Pittsburgh. Investigators also found that because insulin resistance predicts heart disease, “it may explain the longstanding observation that in type I diabetes, kidney disease predicts heart disease. In other words, insulin resistance may be the ‘common ground’ for both complications.”65
Early detection of insulin resistance may, therefore, help prevent potentially serious complications that may result from metabolic disorders, including type I and II diabetes, dyslipidemia, hyperuricemia, and hypertention.
Somatomedin-C (insulin-like growth factor/IGF-1)
IGF-1 is critical in mediating the growth of muscle and other tissues, and normal levels steadily increase until 12-15 years of age, and then begin to decline. Up to one-third of skeletal muscle mass and strength is lost between the ages of 30 and 80.66 A study by Barton-Davis et al showed that IGF-1 overexpression in the muscle cells of mice can preserve the characteristics (morphological and functional) of the skeletal muscles of old mice such that they are equivalent to those of young adult muscles.66 Ruiz-Torres et al showed that when IGF-1 levels in older (over 70) males were similar to levels in younger males (up to 39 years), the older males do not show age-dependent decreases in serum testosterone and lean body mass, nor increases in fat body mass.67
Low levels of IGF-1 have been implicated in the development of atherosclerosis. Van den Beld et al found that high free IGF-1 concentrations appeared to be correlated with reduced risk of atherosclerosis, suggesting that IGF-1 (along with endogenous testosterone and estrone) may play a protective role in the development of atherosclerosis in aging men.68
A study by Carro et al suggests a role for IGF-1 as a neuroprotective hormone. Data show a correlation between lower levels of IGF-1 and higher levels of amyloid-B accumulation in the brains of Alzheimer’s patients. In studies of mutant mice, high amyloid-B levels are seen when serum IGF-1 levels are low. Conversely, the amyloid-B burden can be decreased by increasing levels of serum IGF-1. Investigators suggested that “circulating IGF-1 is a physiological regulator of brain amyloid levels with therapeutic potential.”69
Elevated levels of IGF-1 may be indicative of acromegaly (gigantism) and diabetic retinopathy. Although it has been suspected that high levels of IGF-1 are associated with increased risk of prostate cancer, recent data suggest that IGF-1 may be serving as a tumor marker rather than an etiologic factor for the disease.70 The IGF-1 test (decreased levels) may also be used to evaluate pituitary insufficiency and hypothalamic lesions in children (diagnosis of dwarfism and response to therapy). Low levels have also been found in patients with amyotrophic lateral sclerosis.71
A study on asymptomatic HIV-1-infected subjects tested the hypothesis that oral administration of 3 grams per day of acetyl-L-carnitine (ALCAR) could significantly affect IGF-1 levels. The researchers found that while ALCAR did not raise total IGF-1 levels, it significantly increased the levels of free IGF-1 (the bioactive component of total IGF-1) in treated patients. None of the subjects investigated reported any toxicity directly or indirectly related
to ALCAR administration. Remarkably, all treated patients reported subjectively, without exception, an improved sense of well being by the second to third week of ALCAR therapy.72
Thyroid stimulating hormone (TSH) is secreted by the pituitary gland and serves to control thyroid hormone secretion in the thyroid. Thyroxine (T4) and triiodothyronine (T3, free) are hormones that are released from the thyroid. Iodine that is taken up by the thyroid is incorporated in T3 and T4 (so called because they have three and four iodine atoms, respectively), which serves to increase the body’s basal metabolic rate, regulate growth and development, increase cardiac output, increase the metabolism of cholesterol, increase the number of LDL receptor sites in the liver, and inhibit TSH secretion.
Normally, a decrease in T3 and T4 stimulates TSH release from the pituitary that, in turn, stimulates T3 and T4 production and secretion, and growth of the thyroid gland. When T3 and T4 levels are increased, TSH production is shut down via negative feedback channels.
When TSH, T3, or T4 levels fall above or below normal, this is referred to as hypothyroidism (low thyroid activity) or hyperthyroidism (increased thyroid activity, also called thyrotoxicosis). Overt hyper- or hypothyroidism is generally easy to diagnose, but subclinical disease is a bit more elusive.
In the National Health and Nutrition Examination Survey (NHANES III), hypothyroidism was found in 4.6% (4.3% mild and 0.3% clinical disease) of a cross-sectional population in the US and hyperthyroidism in 1.3% (0.5% clinical and 0.7% mild) of the same study group. Because mild (or “subclinical”) symptoms may be nonspecific (or absent) and progress slowly, and thryroid functions are not routinely screened, people with mild hyper- or hypothyroidism may go undiagnosed. Undiagnosed mild disease may progress to clinical disease states. People with hypothyroidism and elevated serum cholesterol and LDL have an increased risk of atherosclerosis.
Mild hypothyroidism (low thyroid gland function) may be associated with reversible hyper-cholesterolemia (high blood cholesterol) and cognitive dysfunction, as well as such nonspecific symptoms as fatigue, depression, cold intolerance, dry skin, constipation, and weight gain. Mild hyperthyroidism is often associated with atrial fibrillation and reduced bone mineral density and nonspecific symptoms such as fatigue, weight loss, heat intolerance, nervousness, insomnia, muscle weakness, dyspnea, and palpitations, among others.
Measurement of TSH is the best test for assessing thyroid function. Currently, the American Thyroid Association recommends TSH testing beginning at age 35, and every five years thereafter.73 Comparing the ratios between TSH, T3, and T4 blood levels, though, may elucidate definitive diagnosis. This is extremely important, given that the majority of people with mild hypo- or hyperthyroidism are asymptomatic, and levels of thyroid hormones may be depressed or elevated only slightly.
Although the normally “accepted” upper range for TSH is 5.50 mcIU/mL, investigations have shown that blood levels equal and greater than 2.0 mcIU/mL may actually indicate adverse health effects:
On the positive side, when TSH levels are 2.0-4.0 mcIU/mL, cholesterol levels decline in response to T4 therapy.76
The table below summarizes characteristic thyroid panel results from persons with overt or mild hypo- or hyperthyroidism.
Free T3 is valuable in confirming the diagnosis of hyperthyroidism when an elevated free or total T4 level is found. Abnormal concentrations may be seen in T3 toxicosis in the presence of normal T4 levels.