- CaffeineCaffeine: Caffeine is reported to raise natural melatonin levels in the body (787), with a more pronounced effect in nonsmokers (788), possibly due to effects on the liver enzyme cytochrome P450 1A2 (886). It has been proposed that caffeine may increase the bioavailability of endogenous melatonin (887). Caffeine may also alter circadian rhythms in humans, with effects on melatonin secretion (788). It has been reported that caffeine reduced the onset of nighttime melatonin levels for women in the luteal phase, but had little effect on melatonin levels for oral contraceptive users (888). Another human study has shown that a single dose of 200mg of caffeine reduced natural melatonin levels (786), though a more recent human study using a twice-daily dose of 200mg of caffeine over seven days found a lack of effect on nighttime salivary melatonin (889).
- CholesterolCholesterol: There is some evidence of increases in cholesterol levels and atherosclerotic plaque buildup in human research (757) and animal research (759; 760). In contrast, there are also reports of decreases in cholesterol levels in animal research (758) and decreased triglyceride and LDL cholesterol levels in human research (761; 762; 609).
- GlucoseGlucose: Elevated blood sugar levels (hyperglycemia) have been reported in patients with type 1 diabetes (insulin-dependent diabetes) (382; 383), and low doses of melatonin have reduced glucose tolerance and insulin sensitivity (384; 385). In patients with type 2 diabetes mellitus who had a suboptimal response to the oral hypoglycemic agent metformin, melatonin and zinc acetate administration improved impaired fasting and postprandial glycemic control and decreased the level of glycated hemoglobin (386; 387). However, in other research, melatonin supplementation was found to lack an effect on measures of glucose homeostasis (763).
- Natural melatonin levels (decreases)Natural melatonin levels (decreases): Multiple drugs are reported to lower natural levels of melatonin in the body. It is not clear that there are any health hazards of lowered melatonin levels, or if replacing melatonin with supplements is beneficial. Examples of drugs that may reduce production or secretion of melatonin include nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen (Motrin®, Advil®) or naproxen (Naprosyn®, Aleve®) (776; 777); beta-blocker blood pressure medications, such as atenolol (Tenormin®) or metoprolol (Lopressor®, Toprol®) (779; 780); and medications that reduce levels of vitamin B6 in the body, such as oral contraceptives, hormone replacement therapy, loop diuretics, hydralazine, and theophylline (781; 782; 783; 784). Anesthesia using 7% sevoflurane decreased melatonin blood concentrations (785). Asthmatics may have lower levels of endogenous melatonin (809; 810). Melatonin levels in serum decreased noticeably with propranolol treatment (778). Other drugs that may reduce melatonin levels (by inducing P450 1A2) include the following: carbamazepine, insulin, 3-methyl cholanthrene, modafinil, nafcillin, nicotine, omeprazole, phenobarbital, phenytoin, primidone, rifampin, and ritonavir, according to anecdotal information.
- SevofluraneSevoflurane: In human research, sevoflurane resulted in a reduction of postoperative plasma melatonin levels (974).
- VerapamilVerapamil: Verapamil increased urinary melatonin excretion significantly (by 67%), but left excretion of 6-sulphatoxy-melatonin unaffected in healthy adults infused with calcium as a model for hyperkalemia (791).
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The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.