The story of super-supplements – truth or fiction?
Although my usual nutritional message is “optimum diet, no need for additives or multivitamin preparations” and nobody needs extra vitamin C if they eat fruit and vegetables… as far as anti-ageing is concerned, to get potent anti inflammaging activity you need a supplement.
For example, to reach the recommended daily intake of 800-1000mg of quercetin takes more onions, coffee, dill etc than any of us want to consume. Similarly, curcumin (the potent anti-inflammatory agent in turmeric) is very poorly absorbed from food and only a supplement will make any impact [and avoid a very yellow mess in your kitchen].
Supplements are not a substitute for being slim and active - the major influences on longevity. If you are overweight and sedentary then tackle that as well, please! However these agents may help you in weight reduction, blood pressure reduction and lipid normalisation and have other specific effects that you consider valuable.
Remember: as outlined before (see previous InfoSheets) ‘vitamin’ D, magnesium and B12 are often lacking in over 50’s , are hard to fulfil from diet alone and usually should be added.
Summary of 4 stepsFirst: identify what supplements have value either as anti-inflammatory, Second: clarify what formulation is well absorbed, ie effective blood and tissue levels. Third: locate - is there such a product on the market that you can access. Finally: strategy - what is your approach?
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What supplements work and are therefore worth taking?
Anti-aging activity is anti inflammaging activity and there is evidence to include quercetin, EGCG (extracted from green tea) curcumin, resveratrol, nicotinamide mononucleotide [NMN], fisetin and melatonin on the list.
The evidence for usefulness comes initially from laboratory studies on animals or cell preparations. Then human studies in illnesses where there is a strong inflammatory component such as uveitis [inflammation in the eye], irritable bowel syndrome [IBS], sarcoidosis and Long Covid. All are confirmatory to varying extents. There are a small number of studies of anticancer activity.
These agents have no hazards at the doses suggested.
What strategy? Take everything or a selection?
The different supplements reviewed here work in different ways so covering several mechanisms seems logical. You may also have cost constraints.
Your priority should be NMN as this has a specific impact on one of the hallmarks of ageing, namely deterioration in mitochondrial function [the powerhouse of the cell]. Fisetin and quercetin both have proven cardiovascular impact as well as general anti-inflammaging and anticancer effects. As [in the UK] the available liposomal product is a Fisetin + Quercetin combination I suggest using that and adding 2 x 450mg Quercetin liposomal.
You could stop at these three. However, Melatonin is notably low in over 60s and ‘replacing the reduced output from the pineal may seem logical. It may also be critical to aid sleep function: taking the dose with your evening meal times the chronobiological effect for easy sleep-initiation. It is clear that it also has mitochondrial activity and may be synergistic [additive] with the other agents.
It may be that some of the other agents have specific effects on certain cancers [either preventive or therapeutic] or on eye disease, see below. Resveratrol has specific impact in inflammatory bowel conditions and curcumin has both general and antidepressant effects.
Note Carefully! Formulation is important.
The formulation ie type of preparation determines absorption, bioavailability [how much of a dose taken gets to the tissues] and duration of action. Is it a liquid, a tablet, a powder, a depot injection or a clever delivery system such as a phytosomal transformation[1]? For example, curcumin is vastly enhanced by use of small particle formulations such as the phytosomal structure trade-named the ‘Meriva’ process or the reformulation in the product Curcuwin. Similarly Resveratrol is only useful when micronized.
Curcumin
Dose & formulation: Meriva formulation 1.8G [3 capsules of 600mg] daily or Curcuwin 1500mg [3x 500mg]
Product examples: Meriva formulation by Thorne or Intelligent Labs; Curcuwin, by Allergy Research Group or Nutricology
Actions: In the dose suggested, Curcumin has anti-inflammatory, antioxidant, antimicrobial and anticancer properties. It supresses Inflammatory processes and blood markers in many in many inflammatory disease states eg in eye disease [2], in IBS[3], and in chronic kidney disease patients[4]. It shows promise in various cancer treatment scenarios but with no major studies yet published[5]; it also has antidepressant qualities[6]. No adverse effects have been reported.
Quercetin
Dose & formulation: Lysosomal preparation necessary; take 800-1000mg daily [see note about Fisetin+ Quercetin combo]
Product examples: Liposomal Quercetin Supplement 400mg [eg iPerk brand]
Actions: Quercetin has effects on cardiovascular indices including blood pressure[7], blood lipids and metabolic syndrome [in other words hypertension, hyperglycaemia and insulin resistance, central obesity, and hyperlipidaemia] if 500mg or more is used [8]. It has been successfully trialled using 500mg daily in Rheumatoid Arthritis [9] and in sarcoidosis using 2G daily but this was not a liposomal or enhanced absorption formulation, hence my suggestion of the dose above[10].
EGCG [Epi-gallo catechin gallate: the main active infredient of Green tea extract]
Dose & formulation: Aim for 750-800mg daily. Not less than 350 mg daily to get impact. There is high interindividual variation in absorption of this agent after oral administration[11]. The use of nanoparticles can improve absorption [12]. Doses greater than 800mg daily may have unwanted side effects[13].
Product examples: There is no obvious enhanced delivery product available in the UK: One Planet Nutrition Nano EGCG 250mg is shippable from the USA. Or accept a high dose ‘standard ‘preparation for the moment.
Actions: Good laboratory data shows anticancer activity and effectiveness in reducing inflammation[14]. An RCT of 150mg daily vs placebo reduced triglycerides and Blood Pressure [15]. A trial of 850mg vs placebo showed weight loss and consistent decreases in total cholesterol and LDL plasma levels after 12 weeks of high-dose EGCG treatment without any adverse effects[16].
Fisetin
Dose & formulation; Take 300-1000mg daily of an enhanced delivery system. A liposomal formulation or a hydrogel enhances availability[17], as do various nanotechnology modifications.[18].
Product examples: Fisetin with Quercetin 1200mg [of which 1000mg is Fisetsin] Liposomal Encapsulated. [eg Cestfilo, Yipmai brands]. There do not appear to be UK available enhanced absorption products that don’t contain the Quercetin but with 2 capsules of 400mg that makes 100mg quercetin daily.
Actions: Fisetin is a ‘senolytic’, in other words an agent that potentially improves numerous age-related conditions including frailty, osteoporosis and cardiovascular disease16. There is extensive evidence of anticancer activity in multiple different cancer types in the laboratory[19]. in humans Fisetin 100mg daily reduces inflammation in colorectal cancer[20], can enhance anticancer activity in melanoma[21] and improves outcomes in stroke [22]. In summary, there are benefits in terms of chemoprevention, neuroprotection, cardioprotection, anti-aging and prevention of cellular senescence.
Melatonin
Dose & formulation: Take 10mg ideally 2-3 hours before bed/ with evening meal. It is likely that nano-particulate or phytosomal preparations will have greater absorption as absorption of the basic formulation is poor[23]. There is no good study showing absorption of a particular or an enhanced product I could find.
Product examples: Piping Rock 12mg lozenges. The various spray formulations may be useful but I cannot see a clear recommendation.
Actions: Mainly known as a hormone helpful for stabilising sleep rhythms, it also has anti-inflammatory and anti-aging activity[24]. Research over the last decade into cancer, Alzheimer’s disease, multiple sclerosis, fertility, PCOS, and many other conditions, combined with the COVID-19 pandemic, has led to greater awareness of melatonin because of its ability to act as a potent antioxidant, immune-active agent, and mitochondrial regulator[25]. There are initial indications that the antioxidant and anti-inflammatory actions of melatonin may work together with select polyphenols [e.g., resveratrol, EGCG] for therapeutic indications[26].
Resveratrol
Dose & formulation: Take 500-1000mg of ‘trans’ resveratrol daily. There is some evidence that 2x daily dosing is preferable eg 250-500mg am and pm. Bioavailability is enhanced by micronization[27]. The trans isomer is the active form so this is the one to get ie ‘Resveratrol’ has both inactive ‘cis’ and active ‘trans’ components 50/50.
Product examples: Trans Resveratrol Liposomal, 250 mg MCS Formulas.com; Ascent brand micronized trans-resveratrol powder [5 of their tiny scoops = 500mg]
Actions: Resveratrol has multiple beneficial anti-inflammatory actions [28]. Specifically in human studies, a positive impact on inflammatory bowel disease[29] and ulcerative colitis specifically. In the latter an RCT of 500mg vs placebo showed reduction in disease activity, markers of bowel inflammation and an improvement in QoL[30]. Resveratrol is an effective adjuvant in rheumatoid arthritis at a dose of 1000mg daily[31].
Nicotinamide Mono Nucleotide [NMN]
Dose & formulation: Take 1000mg daily. A microcrystalline formulation is best absorbed and studies using doses of 250-500mg did not demonstrate good blood levels
Product examples: NMN Komprocha [lozenges 2 x 500mg]; Charava brands.
Actions: NMN optimises mitochondrial activity [often depleted in older people]; one of the ‘Hallmarks of Aging”. A RCT against placebo demonstrated good blood levels and no adverse effects. There were significant impacts on the 6 minute walk test and on a composite ‘blood biological age index’ [32]. This is a key ‘must have’ compound.
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