Skin in the Game: Citrus Flavonoid Hesperetin Reverses Skin Aging via CISD2 Activation

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#41

Market Analysis: CELLg8 Hesperidin Capsules

Status: Extremely Limited Availability
Constraint Note: “CELLg8” is a proprietary liposomal delivery system patented by Valimenta Labs. While Valimenta manufactures for many brands (Private Label), very few explicitly market Hesperidin specifically under the “CELLg8” trademark on the consumer-facing label. Most brands use generic “Liposomal” labeling.

Result: Only one product was verified to explicitly utilize the CELLg8 delivery system for Hesperidin and is currently in stock for US shipping. The list below reflects this singular verified source.

Top Sources: CELLg8 Hesperidin Capsules

Rank Product/Brand Name Vendor Total Weight (Unit / Net Active) Total Price (USD) Cost Per 100mg Bioavailable Hesperidin*
1 LIPO Hesperidin – Liposomal Hesperidin Renue By Science 90 Capsules

(27,000 mg Total Hesperidin)		 $49.99 $0.19

Product Details & Verification

1. Renue By Science LIPO Hesperidin

  • Verification: Renue By Science sources its liposomal formulations from the primary CELLg8 manufacturer (Valimenta/Cellure), confirmed via supply chain disclosures and product descriptions in international markets (e.g., Shopee Taiwan descriptions for this specific SKU explicitly cite CELLg8 technology).
  • Stock Status: In Stock (Verified via eBay reseller/Healf; official site stock fluctuates).
  • Form: Capsules (Liposomal Powder in Capsule).
  • Dosage: 300mg Standardized Hesperidin per capsule.
  • Link: Renue By Science LIPO Hesperidin (via eBay/Reseller for Stock Verification) (Note: Direct purchase from RenueByScience.com is often cheaper ~$39.95, but stock varies).

Shipping & Cost Summary

  • Shipping: Free shipping is standard on the verified eBay listing; official Renue site typically offers free shipping on orders over a certain threshold (usually $50+).
  • Bioavailability Note: The cost per 100mg ($0.19) is based on the physical input of Hesperidin. If the CELLg8 delivery system increases absorption by the claimed ~10-20x (common for liposomal C/Glutathione), the effective cost per bioavailable gram would be significantly lower (~$0.02), but this requires speculative extrapolation of clinical data.

Next Step: Would you like me to broaden the search to include generic “Liposomal Hesperidin” supplements (non-CELLg8 specific) to provide a wider range of price comparisons?

#42

Follow-on Prompt:

What is the scientific and clinical evidence that the liposomal formulations of Hesperidin from the primary CELLg8 manufacturer (Valimenta/Cellure) have greater bioavailability than the non-lipisomal versions, how good is that evidence, and what is the level of validation on the level of increased bioavailability of these liposomal formulations of Hesperidin?

Gemini Pro Response

Executive Summary: The Evidence Gap

Direct Answer: There is zero direct, peer-reviewed clinical evidence specifically validating the bioavailability of CELLg8 Hesperidin in humans.

While the CELLg8 delivery system (the “platform”) is validated for other nutrients (Vitamin C, Green Tea, B12), Valimenta/Cellure has not published a specific study on Hesperidin. The claims of “superior bioavailability” for their Hesperidin are extrapolations based on their data for chemically similar polyphenols (specifically Green Tea/EGCG).

Detailed Scientific Analysis

1. The Evidence Hierarchy for CELLg8 Hesperidin

Evidence Level Description Status for CELLg8 Hesperidin
Level 1 Peer-reviewed human trial of CELLg8 Hesperidin vs. Standard Hesperidin NON-EXISTENT
Level 2 Unpublished white paper / Internal data for CELLg8 Hesperidin Likely Exists (Not Public)
Level 3 “Platform” validation (CELLg8 works for other molecules) STRONG (Published)
Level 4 General scientific consensus (Liposomes improve flavonoids) STRONG

2. The “Platform” Extrapolation (The “Proxy” Evidence)

Since direct data is missing, manufacturers (like Renue By Science) rely on “Proxy Validation”—using data from structurally similar molecules to infer efficacy.

  • The Best Proxy: Green Tea Extract (EGCG)

  • Why it matters: EGCG is a polyphenol, chemically similar to Hesperidin (both are large, poorly soluble flavonoid molecules).

  • The Data: A CELLg8 study on Green Tea Extract showed a ~10-fold (10x) increase in plasma concentration of catechins compared to standard extract.

  • The Inference: Because CELLg8 worked exceptionally well for EGCG (another difficult-to-absorb flavonoid), it is scientifically plausible—though unproven—that it would achieve similar results for Hesperidin.

  • The Weaker Proxy: Vitamin C

  • The Data: CELLg8 Vitamin C studies show a ~20-50% increase in bioavailability over standard Vitamin C.

  • Why it’s less relevant: Vitamin C is water-soluble and small; Hesperidin is poorly soluble and large. The mechanism of absorption is different, so Vitamin C data is a poor predictor for Hesperidin efficacy.

3. General Liposomal Validation (Non-CELLg8)

Independent science confirms that generic liposomal encapsulation significantly improves Hesperidin delivery.

  • Bioavailability Problem: Standard Hesperidin has extremely poor oral bioavailability (<25%) because it is unstable in gastric acid and poorly soluble.
  • Liposomal Solution: Studies on generic liposomal hesperidin (not specifically CELLg8) have shown plasma concentrations 2-3x higher than standard powder in animal models.

Final Verification Grade

  • Technology Validation: HIGH. The CELLg8 liposomal manufacturing process (using non-hydrogenated sunflower phosphatidylcholine) is well-regarded and verified by electron microscopy (TEM) to create true liposomes (not just emulsions).
  • Specific Product Validation: LOW. The specific “CELLg8 Hesperidin” combination lacks a dedicated public clinical trial.

Academic Consensus: If you purchase CELLg8 Hesperidin, you are buying a high-quality, validated delivery system (CELLg8) applied to a theoretically ideal candidate (Hesperidin), but the specific “10x” or “20x” absorption claim is an extrapolation, not a measured fact for this specific ingredient.

So, the issue with this specific liposomal formulation is that it seems that they price the product at almost the same level as if the “multiplier” is a proven fact (which it isn’t) and so from a functional standpoint the cost per “100mg bioavailable Hesperidin” may be similar whether you buy the regular powder, or the Lipo Hesperidin that is priced 600% higher than the regular stuff. We “know” that they charge 600% more than the non-LIPO products, and they “say” that its 10X more bioavailable, but there is no 3rd party, independent verification of that claim (businesses are free to claim whatever they want in the supplement world, and its not like the pharma business where people validate their claims).

See below, it seems that the cost per 100mg of “bioavailable hesperidin” (the amount your body actually gets) - is still much, much cheaper via the bulk powder. Sure, you have to take 1 gram to get the equivalent of “100mg of the Lipo formulation”, but swallowing 1 gram vs. 100mg is not a significant difference to me, what I really care about is the Cost/100mg of bioavailable hesperidin.

The Master Comparison Table

Product Raw Cost / 100mg Bioavailability Multiplier (Est.) Effective Cost per Bioavailable 100mg Cost Ratio (vs Bulk)
BulkSupplements Powder (1kg) $0.0053 1.0x $0.0053 1x (Baseline)
BulkSupplements Powder (100g) $0.0170 1.0x $0.0170 3.2x
Doctor’s Best HMC $0.0833 3.0x $0.0277 5.2x
Renue Lipo Hesperidin $0.1851 6.0x $0.0308 5.8x

Full Gemini Pro Deep Search Analysis: https://gemini.google.com/share/f51c7e69afed

#43

Is there a graph or particular paragraph that makes it clear that it is hesperetin that is being increased in plasma or tissue and not hesperidin?

#44

The survey paper I linked above only summarizes the 69 papers on encapsulated Hesperidin they reviewed. Based on that:

  1. With regular Hesperidin, almost no Hesperidin is detected in plasma and/or tissue while Hesperitin and it downstream metabolites are detected corresponding to roughly 20% of the ingested Hesperidin.

  2. With encapsulated Hesperidin, both Hesperidin and Hesperitin is detected in plasma and/or tissue, and the majority is in the form of Hesperidin (including encapsulated Hesperidin), but a substantial fraction of Hesperitin is also detected. The survey paper seems to assume that Hesperidin cannot be converted to Hesperitin in the body, so assumes that some of the encapsulated Hesperidin must leak in the gut and get converted to Hesperitin.

  3. The survey paper at one point cautions that none of the encapsulated Hesperidin formulations reviewed provide for any mechanism (e.g. enzyme added) to convert Hesperidin released in the body to Hesperitin, which may impact the biological efficacy of encapsulated Hesperidin.

  4. The clinical studies using encapsulated Hesperidin, however, show efficacy that seems to exceed what would be expected solely based on measured Hesperitin levels. This suggests that Hesperidin (once it gets into a cell) has similar biological efficacy to Hesperitin. This makes sense since the benzene ring structure of the flavone that is believed to be responsible for the biological benefits is the same in Hesperidin and Hesperitin. The addition of the Rutinose sugar in Hesperidin is unlikely to impair this biological benefit : The Rutinose sugar may actually help by making Hesperidin more stable than Hesperitin (which degrades to smaller metabolites within hours in the body), though it also limits the solubility in water of Hesperidin to 0.01% and hence limits how much Hesperidin can be present in dissolved (active) form in cells.

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#45

Wow, that Gemini AI query is starting to resemble a complicated database query. This makes me think that these AI’s are basically giant databases with a natural language front end. Natural language being more ambiguous than database languages like SQL, may actually make it harder to get precise answers from an AI query than a database SQL query.

The AI query is very dependent (for accurate answers) on the manual annotations added to the training data (e.g. to distinguish science fiction from scientific papers) : These manual annotations are very labor intensive and outsourced to supposedly Ph.D. level annotators in India and other countries, but there is little auditing of the supposed qualifications of these annotators and there are articles saying much of these annotations is actually being done by automated programs!

#46

What are you referring to, please? I can’t find any liquid collagen on Costco’s website.
Some people, like my daughter, don’t mind the taste of bovine collagen. I really do not like it, especially in my coffee. So far I haven’t found a collagen supplement that I can put in my coffee. I used to put it in my protein shakes, but I do not currently make any shakes or smoothies.

#47

I bought it in the Costco store, but they also have it online: Zena Liquid Collagen

It is a fruit flavored liquid and you take 10ml per day (roughly a tablespoon) so the bottle (which costs $34.99) lasts 90 days. I am currently taking 2 tablespoons a day to build up my collagen levels. One drawback is it needs to be refrigerated after opening, so takes up fridge space.

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#48

You can find a hesperetin supplement in the UK, though each capsule contains only 120 mg.

https://www.amazon.co.uk/GlucoRegulate-Supplement-Formulation-Trans-Resveratrol-Hesperetin/dp/B0DLWX6W4P

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#49

How does it taste? Is it sweet? I also have difficulty finding collagen that I I’d like.

#50

Mildly sweet and fruit flavored.

#51

Mildly sweet with 0% sugar - this is what scares me.

#52

Collagen is around 30% glycine so it should taste mildly sweet.

@tananth This lacks vitamin C which is required for collagen synthesis but maybe you take it separately.
BTW the minimum effective dose for collagen (at least for tendons and cartilage) is 15g as shown in Keith Baar’s studies.

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#53

Didn’t know about vit C. Thanks. Is there a better choice for collagen than Zena’s?

#54

The same Keith Baar has tested various collagen products as well as gelatin and they are all equivalent as long as it’s more than 15g and taken with vitamin C. No fancy expensive collagen has shown any advantage. The only recommendation he makes is to avoid collagen from bovine bones if possible as they might be contaminated by heavy metal like lead.
That said any reputable brand that tests its own product is probably OK.

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#55

I am considering Biotin Marine Collagen by Codeage - it includes biotin, vit C and E, and insignificant amount of organic fruit. It’s on Amazon.

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#56

Seems OK but you need 15 capsules! It’s going to be a lot of the other stuff they include.

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#57

15 capsules?! Is it because of 15 g per Keith Baar? I would understand 15 g of protein but 15 g of collagen seems too much. Don’t know what to do.

#58

15g or you are just using the placebo effect. I posted about that already: you need to take at least 15+g of collagen and some Vit C but then you increase collagen synthesis by around 3 times.
image

BTW 15g of protein would be nothing either.

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#59

I believe l heard Keith say in a podcast that the collagen was to aid in connective tissue repair. In that context the collagen was just the “icing on the cake”. The overwhelming majority of the repair and strengthening comes from the isometrics for the particular injury. This was 6 months to a year ago so he may have updated his views and/or refined them.

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