Resveratrol: Anti-Aging Revisited & Bioavailability Concerns

Resveratrol: Anti-Aging Revisited & Bioavailability Concerns

Resveratrol: Anti-Aging Revisited & Bioavailability Concerns

Resveratrol is a natural polyphenol that belongs to a class of compounds called stilbenes that has been studied extensively for its potential health benefits, including anti-inflammatory, antioxidant, anti-aging, cardioprotective, and anticancer properties. It is a versatile molecule that can interact with many different targets in the body, including enzymes, transcription factors, and signaling pathways associated with several aspects affecting the aging process.?

The molecular process of aging is a complex and multifaceted phenomenon that involves various biochemical and genetic changes affecting the cells failure to thrive and ability to repair itself - cellular senescence.?Resveratrol has been shown to modulate this process where cells enter a state of permanent growth arrest, preventing them from dividing and contributing to tissue regeneration. In addition, it’s beneficial effects include modulation of various cellular processes including cell proliferation, apoptosis, and autophagy. Autophagy plays an essential role in maintaining cellular homeostasis by removing damaged or unwanted cellular components. Its dysregulation is implicated in the aging process, as autophagy declines with age that contributes to accumulation of damaged cells, impaired cellular function, and the development of age-related diseases.?Activation of autophagy can help to alleviate symptoms and potentially treat certain diseases and also plays a role in the regulation of cellular senescence.

Resveratrol & Aging

One of the proposed mechanisms of action for the anti-aging effects of resveratrol is its ability to activate the protein SIRT1, which is thought to be involved in cellular metabolism and aging.?However, there is some controversy over whether resveratrol actually has this effect. While some studies have found that resveratrol activates SIRT1 and extends lifespan in animal models, other studies have failed to replicate these findings or have suggested that resveratrol may not directly affect SIRT1 at all.?More recent research suggests that resveratrol may exert its effects through other mechanisms, such as by activating other proteins or pathways that are involved in cellular metabolism and aging. Therefore, the exact relationship between resveratrol and SIRT1 is still a topic of ongoing research and debate in the scientific community.

In more recent studies, researchers have been trying to identify the molecular target of resveratrol that induces autophagy and SIRT1, AMPK, PDE, and PI3K were all suggested as potential targets, but the authors found that resveratrol directly inhibits mTOR (mechanistic target of rapamycin) activity.?The mTOR pathway is an intracellular signaling conduit that plays a critical role in regulating cellular response to various environmental and nutritional cues. It has been implicated in the aging process because it is a key regulator of cell growth and metabolism, which are both critical processes that decline with age. Studies suggest that mTOR activity may increase during aging, leading to a variety of age-related diseases and impairments. In animal studies decreased activity has been found to increase life span in animals and is also associated with cellular senescence. In relation to lifespan, senescent cells accumulate in various tissues during aging and contribute to tissue dysfunction and disease.?Studies have suggested that resveratrol can inhibit mTOR signaling, particularly the mTORC1 complex, by activating AMP-activated protein kinase (AMPK), which is an upstream regulator of mTOR. Activation of AMPK leads to the inhibition of mTORC1, which in turn inhibits protein synthesis and promotes autophagy.?

Therapeutic Challenges With Resveratrol Bioavailability

One of the major challenges associated with the use of resveratrol as a dietary supplement or therapeutic agent is its poor bioavailability. Resveratrol has a low oral bioavailability, meaning that only a small fraction of the ingested compound reaches the target tissues where it exerts its effects.?Several factors contribute to its low bioavailability and accessibility, including its poor solubility in water, rapid metabolism in the liver, and limited absorption from the gut.?Studies show that extensive metabolism in the intestine and liver results in an oral bioavailability of resveratrol considerably less than 1% and dose escalation does not appear to alter this significantly! This not only presents a problem for attaining a therapeutic effect when taking resveratrol, but also an issue for consumers who are paying for

The low oral bioavailability of resveratrol can present several problems for consumers, including:

1. Reduced effectiveness: The low bioavailability of resveratrol means that only a small amount of the compound actually reaches the tissues to exert its beneficial effects in the body.
2. Inconsistent dosing: Because the amount of resveratrol that is absorbed into the bloodstream can vary widely from person to person, it can be difficult to ensure consistent dosing when taking resveratrol supplements.
3. Cost:?To achieve a therapeutic dose of resveratrol, consumers may need to take large amounts of supplements or consume significant quantities of resveratrol-rich foods, which can be expensive.
4. Safety concerns: In high doses, resveratrol may have potential side effects or interact with medications, so it is important to use caution when taking supplements containing large amounts of resveratrol.

To address these issues, some manufacturers have developed resveratrol supplements that use alternative forms of the compound that are more bioavailable or that are designed to improve absorption or both. Various strategies have been proposed to improve the accessibility of resveratrol to cells, but one of the most significant and efficient is the use of self emulsifying dietary delivery systems (SNEDDS) developed by Verdant Nature.?The use of SNEDDS technology to enhance bioavailability in the pharmaceutical industry is not a recent development and has been validated through numerous studies over the past few decades. SNEDDS formulations, including those containing resveratrol, have been successfully utilized in various applications. In addition, SNEDDS is a more advanced delivery system that uses smaller droplet sizes, more stable formulation, bypasses liver degradation, greatly improves absorption and accessibility, and improves safety and efficacy of compounds, both lipophilic and hydrophilic, to cells. Unlike the pharmaceutical preparations of SNEDDS that may utilize Tween or SPAN polysorbates, Verdant Nature utilizes clean label, nonGMO, health food trade friendly ingredients in its VN-SNEDDS? ingredients including resveratrol (ResveraSol?).?Using permeation studies to validate the greatly enhanced solubility, permeation, and bioavailability of their VN-SNEDDS? ResveraSol?, companies can now use less material to achieve better accessibility of resveratrol to cells of the body.

References

Park D, Jeong H, Lee MN, Koh A, Kwon O, Yang YR, Noh J, Suh PG, Park H, Ryu SH. Resveratrol induces autophagy by directly inhibiting mTOR through ATP competition. Sci Rep. 2016 Feb 23;6:21772. doi: 10.1038/srep21772. PMID: 26902888

?Gong C, Xia H. Resveratrol suppresses melanoma growth by promoting autophagy through inhibiting the PI3K/AKT/mTOR signaling pathway. Exp Ther Med. 2020 Mar;19(3):1878-1886. doi: 10.3892/etm.2019.8359. Epub 2019 Dec 20. PMID: 32104244

Almeida L, Vaz-da-Silva M, Falc?o A, Soares E, Costa R, Loureiro AL, Fernandes-Lopes C, Rocha JF, Nunes T, Wright L, Soares-da-Silva P. Pharmacokinetic and safety profile of?trans-resveratrol in a rising multiple-dose study in healthy volunteers.?Mol Nutr Food Res.?2009;53(Suppl 1):S7–S15. doi:?10.1002/mnfr.200800177.

Teófilo Vasconcelos,?Multicomponent self nano emulsifying delivery systems of resveratrol with enhanced pharmacokinetics profile?Eur J Pharm Sci.?2019 Sep 1;137:105011.doi: 10.1016/j.ejps.2019.105011.?Epub 2019 Jul 19.

Gurinder Singh,?Trans-resveratrol self-nano-emulsifying drug delivery system (SNEDDS) with enhanced bioavailability potential: optimization, pharmacokinetics and in situ single pass intestinal perfusion (SPIP) studies, Drug Deliv.?2015;22(4):522-30. doi: 10.3109/10717544.2014.885616.?Epub 2014 Feb 11.