…article continued:
The final component involves the clinical use of NHPs (Table 4) that work similarly to pharmaceutical interventions used to mitigate AO represented by high cholesterol (i.e., an abnormal cholesterol profile), metabolic-based diseases (e.g., insulin resistance and obesity), oxidative stress, inflammation, and/or chronic pain. All of these medical problems contribute immeasurably to the burdens of chronic stress and should be managed aggressively. Specific NHPs will be highlighted here though clinicians are certainly encouraged to consider many more NHPs when attempting to lessen the pathophysiological effects associated with AO, and the consequential increased morbidity and premature mortality that normally follows. These NHPs have a superior adverse effect profile compared to commonly prescribed pharmaceutical interventions (e.g., statins and metformin), but several of them (i.e., berberine, curcumin extract, and resveratrol) can sometimes cause symptoms such as gastrointestinal upset, flatulence, constipation, and/or nausea. The published data is strongest for berberine, pantethine, and palmitoylethanolamide, while both curcumin extract and resveratrol require more clinical trials, systematic reviews, and meta-analysis to better support the indications listed in the table.
| TABLE 4 | ||||
| Treatment | Primary Indication | Pharmacologic mechanisms of action | Suggested Daily Dose | References |
| Berberine | Cholesterol modification and insulin resistance | Insulin sensitization; increases glucose uptake; enhances glucose metabolism; stabilizes LDL receptor mRNA; and inhibits lipid synthesis within hepatocytes | 500-1500 mg | 65-68 |
| Curcumin extract (80-95% curcuminoids) | Chronic pain (i.e., joint arthritis), inflammation, oxidative stress, and insulin resistance | Down-regulates nuclear factor-kappa B; modifies proinflammatory cytokines such as interleukin production, phospholipase A2, cyclooxygenase-2, and 5-lipoxygenase; reduces tumor necrosis factor; reduces inducible nitric oxide synthase; protects against advanced glycation as well as collagen crosslinking; and inhibits osteoclastogenesis | 1000 mg | 69-73 |
| Pantethine | Cholesterol modification | Increases coenzyme A levels in cells; inhibits acetyl-CoA carboxylase and HMG-CoA reductase; and favorably modifies lipoprotein metabolism | 900 mg | 74,75 |
| Palmitoyl-ethanolamide | Chronic pain (irrespective of etiology) | Acts as a congener of the endocannabinoid anandamide; agonism of peroxisome proliferator-activated receptor-α; inhibits the release of proinflammatory mediators such as cyclooxygenase, and inducible and endothelial nitric oxide synthase; reduces mast cell migration and degranulation; and reduces over-activation of astrocytes and glial cells | 1200 mg | 76-78 |
| Resveratrol | Inflammation, oxidative stress, and insulin resistance | Too numerous to note, but includes interactions with a large number of receptors, kinases, and other enzymes; and stimulates the activities of sirtuin 1 and adenosine monophosphate-activated protein kinase | 1000 mg | 79-82 |
