Just a reminder that the thyroid is affected by adrenals, as we have been emphasizing, check for adrenal dysfunction first: A reminder to Treat Upstream So do you have patients who are stressed and have cold hands and feet and other hypothyroid symptoms? That may be adrenal dysfunction. Think about treating upstream.
Dr. Chris D. Meletis Executive Director Institute for Healthy Aging copyright Dr. Meletis 2011
The information shared in this presentation is educational only. Consulting with ones personal physician and pharmacist is essential prior to changing medications or adding supplements to current medications taken.
The information shared here is not intended as either diagnosis or treatment.
Drug side effects are the fourth leading cause of death in the United States.
According to an article published in the Journal of the American Medical Association, approximately 106,000 Americans die and 2,000,000 suffer from severe reactions every year from drugs prescribed in hospitals.
Lazarou J., Pomerantz, B., Corey, P., Incidence of Adverse Drug Reactions in Hospitalized Patients, A Meta-analysis of Prospective Studies, JAMA, April 15, 1998, 279(15): 1200-1205.
A study published in 2005 showed that many Americans were not meeting the U.S. Recommended Dietary Allowances for a number of nutrients: 73 percent of people were not getting enough zinc in their diets, 65 percent were deficient in calcium intake, 62 percent were low in magnesium, 56 percent in vitamin A and 54 percent in vitamin B6.
A new concern in health care is that, on top of already marginal nutrient intake for some people, nutrient depletion is worsened by some of the common medications taken by many Americans.
In March, the FDA published a safety announcement on the risk of magnesium deficiency in anyone taking proton pump inhibitors for more than a year.
And while some people may be protected by taking a daily magnesium supplement, studies suggest that about 25 percent of people who take PPIs are unable to normalize their blood magnesium level with a supplement -- they have to stop the drug in order to return their blood magnesium levels to normal.
Long-term reduction in calcium absorption from PPIs also can affect your bone health and increase your risk of osteoporosis.
Magnesium deficiency can contribute to anxiety, restless leg syndrome, insomnia and muscle spasm, life-threatening arrhythmias.
Nutrition and heart failure: impact of drug therapies and management strategies. Nutr Clin Pract. 2009 Feb-Mar;24(1):60-75. Abstract Nutrition impairment commonly occurs in patients with heart failure and affects disease progression. Vitamin and mineral deficiencies are associated with early mortality, particularly in patients classified as cachectic. Guideline-based therapies approved for heart failure, such as loop diuretics, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, aldosterone antagonists, and beta-adrenergic blockers, can lead to electrolyte abnormalities and predispose to some vitamin and micronutrient deficits. copyright Dr. Meletis 2011
Clinical trial evidence in support of supplementary vitamin and mineral therapies for heart failure patients is limited with the exception of documented calcium and possibly vitamin D, thiamine, and coenzyme Q10 deficiencies.
Limited human data suggests that diuretics may increase excretion of folic acid. Reduced red blood cell folate levels, possibly contributing to increased homocysteine levels, a risk factor for cardiovascular disease, were found in one group of people taking diuretics for six months or longer.
Based on in vivo evidence , triamterene (potassium sparing diuretic) inhibits the intestinal absorption of folic acid in a dose-dependent manner.
17 hypertensive patients receiving long-term diuretic therapy vs . 17 hypertensive patients not taking diuretics
Mean homocysteine concentration for patients taking diuretics (17.87 +/- 1.72 micromol/L) vs. (10.31 +/- 0.99 micromol/L).
Mean RBC folate concentration for patients taking diuretics
(281.01 +/- 17.56 ng/mL) vs. lower (430.85 +/- 28.58 ng/mL).
Chronic diuretic use is associated with a significant increase in serum homocysteine concentration, a significant decrease in RBC folate concentration , and no significant change in concentrations of vitamins B6 and B12.
Based on human evidence, HMG-CoA reductase inhibitors (e.g. lovastatin) lead to a decreased concentration of CoQ10 on human studies , CoQ10 concentrations decreased in patients treated with pravastatin and lovastatin or pravastatin and simvastatin.
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Thiamine: Loop diuretics , particularly furosemide (Lasix®), also another drug Bumex; have been associated with decreased thiamine levels in the body by increasing urinary excretion (and possibly by decreasing absorption and increasing metabolism).
Animal evidence suggests that the increase in urinary excretion of thiamine may be associated with furosemide, acetazolamide, chlorothiazide, amiloride, and mannitol.
Can J Clin Pharmacol. 2003 Winter;10(4):184-8. Thiamine deficiency in congestive heart failure patients receiving long term furosemide therapy.
Based on human evidence, loop and thiazide diuretics may increase urinary
Mean hair zinc was found to be significantly lower in 20 mild hypertensive patients treated with thiazides for 6-36 months than in 19 mild hypertensive patients who had not been given diuretics for at least six months before study.
Chronic diuretic treatment can result in zinc deficiency through enhanced urinary excretion of zinc.
GLA at Work—For The Good of the Body High blood pressure (Hypertension) In one study, men with borderline high blood pressure who took 6g of blackcurrant oil had a reduction in diastolic blood pressure compared to those who took placebo. Another study examined people with intermittent claudication, pain in the legs while walking that is caused by blockages in the blood vessels. Those who took GLA combined with EPA had a reduction in systolic blood pressure compared to those who took placebo. copyright Dr. Meletis 2011
Based on human study, melatonin changes after antidepressant use may be due to pharmacological action of these drugs on melatonin secretion.
After treatment with selective serotonin reuptake inhibitors (SSRIs), levels of 6-sulphatoxymelatonin (aMT6s), the main melatonin urinary metabolite, increased. In human trial, fluoxetine (Prozac) reduced melatonin levels.
A six-week case-controlled study with repeated overnight blood sampling was conducted. Ten patients fulfilling the criteria for major depressive disorder, seasonal type, with a 29-item Hamilton Depression Rating Scale (HDRS) score of at least 20 were compared with ten age- and sex-matched healthy controls in a clinical laboratory. The effects of fluoxetine (20 mg/day) on the HDRS and melatonin concentration were measured.
RESULTS: Fluoxetine significantly reduced melatonin levels in both groups. There was no significant difference in melatonin secretion between the groups.
CONCLUSIONS: The effect of fluoxetine differs from tricyclics and fluvoxamine (Luvox), both of which increase melatonin.
According to a review, hyponatraemia may be a possible reaction to treatment with selected serotonin reuptake inhibitors (SSRIs) and measurement of serum electrolytes may be recommended, particularly in patients over the age of 65.
Some oral diabetic medications such as chlorpropamide, glimepiride, glipizide, glyburide (Micronase, Diabeta, Glynase Prestab), tolazamide, tolbutamide, and acetohexamide, may reduce the levels of coenzyme Q10 (CoQ10).
Based on secondary sources, biguanides may reduce CoQ10 concentrations.
vitamin B12 deficiency in a metformin-treated diabetic patient.
Vitamin B12 deficiency may be induced by long-term use of metformin, which may in turn lead to hyperhomocysteinemia.
Hyperhomocysteinemia may increase the risk of vascular thrombosis in diabetic patients, when metformin is used and a homozygous methylenetetrahydrofolate reductase (MTHFR) .
Our findings highly suggested the role of metformin in causing vitamin B12 deficiency, which may serve as an additional risk factor for venous thrombosis in diabetic patients. Our report also highlights the need to check vitamin B12 levels during metformin treatment.
Based on animal evidence, glutathione may be reduced by acetaminophen in a dose-dependent manner.
A review discussing acetaminophen-related toxicity explains that the hepatic glutathione stores are depleted to combine with acetaminophen’s toxic metabolite. According to the review, for such toxicity, N-acetylcysteine (NAC) may be recommended and effective if given within the first 15 hours of overdose.
Diazepam clearly affected pineal melatonin biosynthesis and plasma melatonin levels. Diazepam reduced the pineal melatonin content (by a factor of 2) and the activity of N-acetyltransferase (NAT) (by a factor of 3.5) , as well as plasma melatonin levels (by a factor of 1.5).
Based on human evidence, oral contraceptives (birth control pills) may impair folate metabolism producing depletion . BUT the effect is unlikely to cause anemia or megaloblastic changes .
There have been cases of megaloblastic anemia in humans, however, with long term use of oral contraceptives. Progesterone based therapy may decrease folate levels, as witnessed in animal study involving chick embryos.
A 34-year-old woman developed megaloblastic anemia and peripheral polyneuropathy following the use of oral contraceptives for 4 years. Low levels of folic acid and vitamin B12 were found. Both the complete recovery after therapy with the vitamins, and the absence of other causes of vitamin B12 and folate deficiency, suggest that the vitamin deficiencies were caused by the oral contraceptives and resulted in the rare combination of megaloblastic anemia and polyneuropathy. The poor response to vitamin B12 alone, and the development of anemia and polyneuropathy 4 months after cessation of vitamin B12 therapy suggest that folate deficiency was the primary problem.
The use of contraceptive pills has been shown to decrease the physiologic levels of six nutrients--riboflavin, pyridoxine, folacin, vitamin B12, ascorbic acid and zinc--and to increase the levels of four others--vitamin C, iron, copper and vitamin A.
The group using oral contraceptive agents (OCA) had significantly lower serum levels of vitamin B12 vitamin as compared to those of the control group.
The OC group had a significantly lower total serum vitamin B12 binding capacity, a lower total transcobalamin 1 level, and a higher transcobalamin 3 level. The fall of serum vitamin B12 in OC users appears to be due to changes in vitamin B12 binders of serum and does not represent vitamin B12 deficiency, giving no justification for vitamin B12 supplementation in users of OCs.
CONCLUSIONS: These findings may be important because selenium is currently believed to offer protective benefits against carcinogenesis. It has been thought that the decrease in serum zinc could be reflected in a reduction of tissue zinc status due to changes in zinc absorption, excretion or tissue turnover. If these changes occur, the dietary zinc requirement would be greater in women using OCP.
Though T4 and T3 are both active as thyroid hormones; T3 is three to five times as active as T4.
T2 and rT3 are not “positively” active.
copyright Dr. Meletis 2011
Liothyronine (T3, R= H) is 3 to 5 times as active as thyroxine (T4, R=I). The extra iodine atom present in T4 causes steric hindrance in binding to the thyroid receptor. This steric hindrance is responsible for the lower activity of T4 . copyright Dr. Meletis 2011
For the Sake of Thirst ? copyright Dr. Meletis 2011
Cimetidine (Tagamet®) and Ranitidine (Zantac®) may reduce the activity of 5'-Deiodinase.
Histamine H2 receptor antagonists have been reported to increase the conversion of T4 into reverse T3 by inhibiting the 5'-Deiodinase enzyme that catalyzes the conversion of T4 into T3.
Perret, G., et al. Effect of a short-term oral administration of cimetidine and ranitidine on the basal and thyrotropin-releasing hormone-stimulated serum concentrations of prolactin, thyrotropin and thyroid hormones in healthy volunteers. A double-blind cross-over study. Pharmacology. 32:101-108, 1986.