More info (and Examine.com has a lot of good detailed information on this topics) - it seems Hesperidin / hesperetin could possibly interact with rapamycin doses / bioavailability - something to dig deeper into if considering it:
That being said, in animal studies oral intake of hesperidin at a dose similar to that used in humans seems to be a very potent cardioprotection agent and is quite protective of the brain in response to various stressors; the protection is antioxidative in nature, but it seems to work through a currently not identified antioxidant responses from the genome. Aside from the protective effects (most notable in the heart and brain, but extend to every organ), hesperidin may be able to reduce a lack of appetite and have minor anti-allergic properties.
Orange peels can actually be used to get the supplemental dosage of hesperidin seen in the human studies, and hesperidin is known to interact with a variety of drug metabolizing enzymes so it should be approached cautiously if also using pharmaceuticals.
Another interesting flavanone, 7,8-Dihydroxyflavone has properties other than what I consider the main benefit which is increasing neurogenesis. They include estrogen suppression, endothelial cell protection, neuroprotection, and squamous cell cancer protection.
âHere we demonstrate that 7,8-DHF administered in drinking water significantly decreases the severity of pathologies in Mecp2 mutant mice, including improvements in life span, body mass, voluntary running wheel distance, hippocampal neuronal nuclei size, and breathing abnormalitiesâ
Suggesting 7,8-dihydroxyflavone as a promising nutraceutical against CNS disorders.
Treatment with the flavonoid 7,8-Dihydroxyflavone: a promising strategy for a constellation of body and brain disorders
Hesperidin, Hesperetin, Rutinose, and Rhamnose Act as Skin Anti-Aging Agents
Aging is a complex physiological process that can be accelerated by chemical (high blood glucose levels) or physical (solar exposure) factors. It is accompanied by the accumulation of altered molecules in the human body. The accumulation of oxidatively modified and glycated proteins is associated with inflammation and the progression of chronic diseases (aging). The use of antiglycating agents is one of the recent approaches in the preventive strategy of aging and natural compounds seem to be promising candidates. Our study focused on the anti-aging effect of the flavonoid hesperetin, its glycoside hesperidin and its carbohydrate moieties rutinose and rhamnose on young and physiologically aged normal human dermal fibroblasts (NHDFs). The anti-aging activity of the test compounds was evaluated by measuring matrix metalloproteinases (MMPs) and inflammatory interleukins by ELISA. The modulation of elastase, hyaluronidase, and collagenase activity by the tested substances was evaluated spectrophotometrically by tube tests. Rutinose and rhamnose inhibited the activity of pure elastase, hyaluronidase, and collagenase. Hesperidin and hesperetin inhibited elastase and hyaluronidase activity. In skin aging models, MMP-1 and MMP-2 levels were reduced after application of all tested substances. Collagen I production was increased after the application of rhamnose and rutinose.
Many years ago I used a bitter orange supplement to help with weight loss. Bitter orange was once a rage in the weight loss community. I donât recall it actually being very effective for that. If it was, it would still be a big deal.
FWIW:
A quick look at the supplements available at Amazon shows two major forms of hesperidin supplements: methyl chalcone is a modified form of hesperidin that is often used in dietary supplements due to its enhanced bioavailability and Citrus aurantium, also known as bitter orange, which is believed to have potential weight loss and thermogenic effects.
So, if I decide to try it I will probably go for the methyl chalcone form because of its better bioavailability and I donât need any weight loss or thermogenic effects. I am mainly interested in its possible anti-aging effects.
Renue By Science is planning to release a LIPO version of Hesperidin by Aug or Sep '23 : They already have LIPO Hesperidin in a mixed LIPO product with 150mg Hesperidin + 100mg CoQ10 + 65mg Tr-Resveratrol + 35mg Green Tea Extract. Based on past history their pure LIP0 Hesperidin will have roughly twice the dosage of the combo product (as is the case with their current 200mg CoQ10 or 125mg Resveratrol or 75 mg Green Tea Extra single item LIPO versions), but if you like those additional items as well the 4-in-1 combo is 50% cheaper than buying them individually.
Hesperidin is converted by the gut microflora into hesperetin.
After oral intake of hesperidin, it is able to be hydrolyzed and de-glycosylated by the gut microflora into its aglycone form hesperetin; this mainly occurs in the colon. Once this has occurred, the hesperetin is absorbed into systematic circulation by colonocytes via proton-coupled active transport and transcellular passive diffusion [77]. In addition, plasma hesperetin is further metabolized into other metabolites, including hesperetin glucuronide (H7G, hesperetin-7-O-β-D-glucuronide) and hesperetin sulfate (H7S, hesperetin-7-O-sulfate) in the liver (Figure 2G,H). Our recent studies showed that hesperetin and its metabolite H7S are both able to enhance CISD2 expression [75].
Hesperetin activates CISD2 to attenuate senescence in human keratinocytes from an older person and rejuvenates naturally aged skin in mice
Conclusions
Our results reveal that a pharmacological elevation of CISD2 expression at a late-life stage using hesperetin treatment is a feasible approach to effectively mitigating both intrinsic and extrinsic skin aging and that hesperetin could act as a functional food or as a skincare product for fighting skin aging.
4.3. Natural Compounds That Can Upregulate CISD2 Expression
Several naturally derived compounds have been identified to increase CISD2 gene expression, including hesperetin, curcumin, wild bitter melon (WBM) extract, Îą-eleostearic acid, egg shell membrane (ESM) powder, and hydrated ESM (Table 1 (B)). In addition to hesperetin, which will be discussed in Section 5, the other compounds mentioned above are briefly described below.
Iâll remember that next time I cook hard-boiled eggs. They can also be bought in capsule form.