Promanna: New generation in health ageing

Promanna is a novel combination product of a small number of orally administered active small molecules in a proprietary formulation. It provides protection against DNA-damage and therefore protects the cells of the body. One of the components, Selenium, has been extensively tested in human studies and carries approved health claims by EFSA. The other main ingredients, variants of L-Proline and D-Mannitol in a certain ratio and concentration, have been shown to delay the progression of important symptoms in animal models for premature ageing. In particular slowing down degeneration of the retina, stimulation of growth and survival are relevant effects in the context of ‘healthy ageing’. D-mannitol and L-Proline have also been shown to provide protection against DNA-damage in cultured human cells. L-Proline and D-Mannitol are the main ingredients of the biblical Mannah or ‘heavenly bread’ to which significant health effects were attributed in the Bible as well as in the Quran. Selenium, on the other hand, is a spore-element with strong protective effects against damage of DNA and cells. It has shown several health benefits in well-controlled human studies prompting European authorities to allow the use of several health claims. The combination of these ingredients is novel and based on extensive research performed in The Netherlands. Finally, Promanna contains a number of ingredients, including B-vitamins, that are widely recognized as beneficial for healthy ageing.

Anticipated use

Promanna protects against the accumulation of DNA-damage, which is at the basis of ageing. In particular degeneration of tissues that are sensitive to DNA-damage will be affected by the use of Promanna. These include, brain-tissue, retina (eye) and skin. Use of this product is extremely safe and may, therefore, be broadly used by consumers who have an interest in ‘healthy ageing’ and/or who run a risk of increased accumulation of DNA-damage (for instance related to advanced ageing, high metabolism, unhealthy lifestyle etc.). The product will be delivered as a powder in a sachet containing approximately 6 grams for one dose. Promanna easily dissolves in water, juice, milk etc. and should (ideally) be taken twice a day, around breakfast and around dinner. It has a bitter-sweet taste which most consumers find very acceptable.

Description of ingredients

L-Proline, one of the two active ingredients of Promanna, is an amino-acid which is quite abundant in gelatine, a common nutritional product. It exerts several positive effects in organisms under stress. On the one hand it removes or scavenges molecules (such as oxygen radicals) that cause damage to DNA. On the other hand it plays a role in the regulation of autophagy which is an important process in ageing and regeneration. While other health benefits have been attributed to the consumption of L-Proline (including maintenance of muscle and joint flexibility, formation and repair of bones and skin) these have not yet been documented properly in scientific studies. L-Proline is produced by the body itself, but, apparently, under conditions of stress (often causing extra DNA-damage) additional L-Proline will help to reduce the negative effects of such stress. Human diseases where L-Proline synthesis is impaired are very rare and cause severe symptoms including bone and skin problems, cataracts, and progressive neurodegeneration. Mutant mice, incapable of producing L-Proline exhibit similar degenerative diseases and, in general, suffer from accelerated aging.

L-proline is manufactured through microbial fermentation of sugars originating from vegetable material, followed by isolation and purification of crude L-proline.

D-Mannitol is a sugar (poly-ol) with health promoting effects stretching back to biblical times as the main component of Mannah. It is also a main component of Cordyceps sinensis a Chinese herb which, for centuries, has been used in China to boost energy levels. Recent scientific evidence shows that it affects oxygen-metabolism: not only relevant for the body’s energy metabolism, but also relevant to the generation of DNA-damage. These data are consistent with our recent scientific evidence that suggests that D-mannitol is able to induce cellular pathways that defend cells against the formation of DNA-damage and against the negative effects of DNA-damage. One of these pathways (the NRF2-pathway) is known to act against the formation of DNA-damage and is also known to be de-regulated in neurodegenerative disorders including Alzheimer’s disease and Parkinson’s disease. In recent years it has become an important target in developing new therapies against diseases related to neuronal degeneration (Multiple sclerosis, Alzheimer’s and others).

D-mannitol is also of vegetable origin and is isolated from seaweed in a large-scale automated process delivering very pure product with minor contaminations of other sugars in particular Sorbitol, Maltitol and Isomaltitol.

Selenium is a trace element nutrient that functions as cofactor for several antioxidant enzymes which are produced by the body via the pathway that is activated by D-mannitol. EFSA has approved several health claims for Selenium based on large epidemiologic and controlled studies in humans. Perhaps the most relevant property of Selenium is that it helps to protect DNA against damage by oxidative stress. Just like D-mannitol it acts by supporting and activating the body’s own defence systems. Since its mechanism of action is compelementary to that of D-mannitol and L-proline it make sense to combine these three ingredients into one product.

Just like the other ingredients Selenium is manufactured from a vegetarian source.

Mode of action and scientific evidence

The individual compounds of Promanna have clear and distinct modes of action. While they all have positive effects on DNA-damage protection and health, their effects are additive and the combination of the compounds has distinct advantages over using the compounds separately.

Current evidence suggests that proline acts by regulating several processes, -most notably, autophagy and DNA-repair enzymes- which have been shown to play a role in ageing. Diseases, in animals and humans, where insufficient proline is produced lead to several physiological problems including accelerated ageing. Mannitol, most likely acts by activating several endogenous biochemical pathways (such as NFkb and NRF2) which, in turn, activate enzymes (such as superoxide-dismutase) that neutralize radicals which can damage DNA. In both cases, the net effect is that by reducing the DNA-damage load the ageing process is delayed.

Selenium acts as an essential co-factor for enzymes that neutralize radicals which can damage DNA. The production of these enzymes is activated by the action of D-mannitol and the extra intake of selenium ensures that all enzymes produced can be active in the cell.

Functional positive effects of D-mannitol and L-proline –which, so far, have not been used as nutritional supplements- were measured in an animal model and in human cells with very promising effects. Data are available, on a confidential basis, to interested distributors and professionals.

All ingredients of Promanna were extensively tested for safety and tolerability in a non-clinical and toxicology program in rats and dogs for a period of six and nine months respectively. It was also tested in a human healthy volunteer study. With detailed reports available the product was found to be extremely safe and well tolerated with no significant side-effect even at dosages over 10 times the anticipated dose. Selenium was tested separately in many human studies and found to have an excellent safety profile for the dosages used and recommended.

Positioning of Promanna

All ingredients have official status as allowed nutritional products in the EU and USA and, thus, may be sold on the market without further registration procedures. D-mannitol and L-proline have not yet been evaluated by EFSA for their health benefits in humans. Selenium has been evaluated with a favourable outcome relative to several health claims including the ones proposed for promanna.

The product is particularly well suited for people concerned with DNA-damage in the context of ‘healthy ageing’, but is also relevant for people having a lifestyle known to generate excessive DNA-damage, including endurance athletes, frequent flyers, smokers, people exposed to radiation (including sunlight) and for people exposed to excessive amounts of ‘radical inducing chemicals’ such as cigarette smoke, polluted air, alcohol and certain fatty acids.