Effects of Fermented Papaya Preparation (FPP) on Safety Outcomes in Older Adults - A Short Report of a Placebo-Controlled Clinical Trial.

Fermented Papaya Preparation (FPP®) has shown antioxidative and anti-inflammatory effects in preclinical and clinical aging studies. However, clinical trials are needed to fully evaluate the safety of FPP® in moderate-functioning, generally healthy older adults. In this randomized (9g/day of FPP® or placebo), crossover design study, we enrolled 30 older moderate-functioning older adults (70-100 years old). The participants completed both a treatment and a placebo condition. After eight (8) weeks on each of these regimens (with a 4-week wash-out period in between), participants had their venous blood drawn for assessment of blood chemistries, metabolic outcomes and inflammatory biomarkers. Participants were asked to report any adverse events during the course of the study and complete post-treatment outcome assessments for anthropometric and metabolic outcomes. The major finding related to safety was that there were no adverse changes in blood chemistries and few adverse events in the FPP® condition, which did not differ from placebo (p>0.05). There were no serious adverse effects in either condition. Twenty-nine (29) participants (mean age 78.2±5.3 yrs) completed the study with 94% adherence to the dosing regimen. There were no significant effects of FPP® on anthropometric and metabolic outcomes. In addition, no effects on markers of inflammation were observed. Our trial demonstrates FPP® supplementation is safe and feasible in adults ages 70 years and older. Based on these findings and the positive effects FPP has demonstrated in previous trials, future trials should examine the effects of FPP® in older adults with impaired health status and/or older adults who may have insufficient anti-oxidant protection due to their genetic background.

Inhibition of brown fat activity during hypothalamic stimulation in the rat.

Previous work has shown that low-level electrical stimulation of the ventromedial hypothalamus (VMH) in anesthetized rats produces a sustained decrease (phase 1) in interscapular brown adipose tissue (IBAT) temperature followed by a rise (phase 2) after the stimulus has stopped [Woods, A. J., and M. J. Stock. Am. J. Physiol. 266 (Regulatory, Integrative Comp. Physiol. 35): R328-R337, 1994]. In this study, rat oxygen consumption was found to decrease (24%) and then increase (74%) during phase 1 and 2, respectively. The effect of norepinephrine, alpha-adrenoceptor antagonists, substance P, and neuropeptide Y, with and/or without VMH stimulation, suggested that vasoconstriction was unlikely to account for the phase 1 decreases in thermogenesis and temperature. However, measurement with radio-labeled microspheres showed that IBAT capillary blood flow was reduced by 70% during phase 1, and this, plus a 50% decrease in blood oxygen extraction, indicated that phase 1 could be due to vasodilatation of arteriovenous anastomoses. It was postulated that phase 1 resulted from release of neuropeptides, such as substance P, causing diversion of arterial blood away from IBAT capillaries, thereby increasing convective heat loss and inhibiting heat production during phase 1.

Biphasic brown fat temperature responses to hypothalamic stimulation in rats.

Low-level electrical stimulation (monophasic square-wave pulses: 15 Hz, 7.0 microA, 0.5 ms) of the ventromedial hypothalamus (VMH) in anesthetized rats produced a decrease (phase 1) in interscapular brown adipose tissue (IBAT) temperature that was sustained for as long as the stimulus was applied (2-45 min). A rise in IBAT temperature (phase 2) occurred only after the stimulation had stopped. VMH stimulations ipsilateral and contralateral to a lateral hypothalamic (LH) lesion indicated that the phase 1 response required an intact LH, and denervation of IBAT showed that both phases required an intact sympathetic innervation. Central intracerebroventricular injections of amphetamine and dopamine produced decreases in IBAT temperature similar in magnitude to the phase 1 response to electrical stimulation of the VMH. This, as well as the observation that pimozide blocked phase 1, suggested that dopaminergic pathways were responsible for mediating the phase 1 decrease in IBAT temperature. The peripheral mechanisms responsible for phase 1 are unknown, but a vascular component might explain the unexpected decrease in IBAT temperature seen during sustained VMH stimulation.