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 bio-active 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/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 synthesized (from thyrotropin releasing hormone/TRH) and 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 serve 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, and/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 a study by 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 U.S. 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 hypercholesterolemia (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:
TSH >2.0mcIU/mL increased the 20-year risk of thyroid-induced autoimmune attack.74
TSH >4.0mcIU/mL increased the risk of heart attack.75
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.
Helicobactor pylori, IgG antibodies
Helicobactor pylori (H. pylori) bacteria infect the gastric mucosa (stomach lining), and have been implicated as the etiological agent in some patients with chronic gastritis, and in 80% and 95% of patients with gastric and duodenal ulcers, respectively. Approximately 90% of patients with both types of ulcers are asymptomatic, and left untreated, H. pylori infection may lead to gastric malignancies. (http://www.fpnotebook.com/GI97.htm). The H. pylori antibody test is a highly specific and sensitive test for detection of infection with H. pylori and assessing the efficacy of antimicrobial treatment.
Gamma glutamyl transpeptidase (GGT)
GGT is a biliary enzyme that is useful for diagnosing diseases of the liver and pancreas. It may also be used to distinguish abstinent alcoholics from alcoholics who continue to drink. Levels are commonly elevated in patients with liver inflammation (due to viral hepatitis, alcohol abuse, mononucleosis, cytomegalovirus/CMV, myocardial infarction, diabetes mellitus, neurologic disease, trauma, and sepsis) or obstruction of the bile ducts (from pancreatic disease, gallstones, or tumors). Decreased levels of GGT may be found in hypothyroid patients or in patients with low magnesium levels or hypothalamic malfunction. GGT is a very specific indicator of liver damage or biliary obstruction, and will be the first hepato-biliary marker to indicate any increases in the blood. GGT, CEA, and alkaline phosphatase, used together, are useful markers to detect liver metastasis from the breast and colon. GGT should be tested along with AST and ALT to diagnose liver and biliary dysfunction.
Carcinoembryonic antigen (CEA)
Carcinoembryonic antigen is a substance that is normally produced in the fetal stage of life. Production usually halts before birth, and blood levels are undetectable in healthy adults. CEA can be seen in people who are heavy smokers, and in patients with certain cancers, particularly those of the pancreas, colon, rectum, breast, and lung. A tumor marker, CEA is not used to diagnose disease, but to determine the extent of disease and patient prognosis, and to monitor treatment efficacy. CEA is often the first marker to elevate in response to a cancer relapse and may show up months before patients become symptomatic or show a response with other laboratory tests.
CEA levels may also be elevated in patients with inflammations (i.e., infections, inflammatory bowel disease, and pancreatitis), hypothyroidism, and cirrhosis.
Cancer Antigen (CA) 15-3
CA 15-3 is a tumor-associated serum marker that is highly valuable for monitoring response to treatment of breast cancer, and as a possible indicator of disease recurrence. Some investigators have shown that CA 15-3 is rarely elevated in the early stages of breast cancer. CA 15-3 is not used to diagnose disease, particularly as patients with breast carcinoma have antigen levels in the same range as healthy individuals.
Increased CA 15-3 levels may also be seen in cancers of the pancreas, lung, ovary, and liver, as well as in (non-malignant) hepatitis and cirrhosis.
Women in particular are at increased risk for development of osteoporosis (decrease in bone density). At risk are persons of low body weight (relative to height), cigarette smokers, alcohol abusers, individuals with low dietary calcium and vitamin D intake, women undergoing early menopause, young women who are not menstruating, and persons not getting enough weight-bearing exercise. Family history and advanced age are also risk factors. People with osteoporosis are at increased risk for bone fractures, which may lead to chronic pain, disability, and even death. Osteoporosis can be prevented by determining risk through laboratory testing of biochemical markers, and then taking the proper steps (diet, exercise, drug therapy, supplementation) to reduce bone loss.
A highly accurate and inexpensive test of bone resorption (breakdown) is Pyrilinks-D or Dpd (deoxypyridinoline), which involves testing of the second voided urine specimen of the day. DpD, along with pyridinoline (Pyd), forms the rigid crosslinks of mature Type I collagen in bone. During bone resorption, DpD is released into the circulation and is excreted unmetabolized in the urine. Increased levels of Dpd in the urine have been correlated to risk of osteoporosis77 and response to hormone replacement therapy.78
Interleukin-6 (IL-6), which is produced in a variety of tissues including bone, stimulates the differentiation and proliferation of osteoclasts (cells that play an active role in bone resorption), which may then lead to increased bone resorption. Increased blood levels of IL-6 have been found to be a major predictor of bone loss in postmenopausal women, specifically through the first postmenopausal decade.79 Increased levels have also been seen in women with hyperparathyroidism with subsequent bone loss.80
Biochemical markers for bone remodeling (growth) can assess a patient’s status or risk for significant decrease in bone mass by providing a means of measuring bone turnover. In a clinical trial of 7,598 women, increased Ntx (bone resorption marker, see table below) was associated with increased risk of hip fractures.
While bone densitometry can give an accurate snapshot of bone density, one to two years between evaluations are necessary to detect a bone loss of only 3% to 5%. Changes to bone metabolism can be assessed using biochemical markers beginning three to six months after initiation of therapy.
Bone markers may be classified as bone formation or resorption. Resorption, the breaking down of collagen, occurs prior to bone formation, and biochemical markers provide a direct indication of efficacy of antiresorptive therapy. No change in marker levels may indicate therapy is ineffective (or the patient is noncompliant). An increase in marker levels indicates bone loss (ineffective therapy), a decrease in marker levels indicates therapy is working. View information on some of the most important bone formation and resorption markers.