PLEASE NOTE: This page is quite long and is an abridged version (for space reasons) from the printed guide. You can find the complete appendix in a more mobile-friendly format at Appendix II: LifeSpan Essentials
Polyphenols are plant-based nutrients that evolved as a natural defence against plant pathogens and protection from ultraviolet radiation. They are the most abundant antioxidants in our diet, and evidence for their role in the prevention of degenerative disease in the human population is strong. Polyphenols represent an immense variety of compounds and are divided into four main categories: flavonoids, phenolic acids, stilbenes, and lignans. The two most prominent are the flavonoids and the phenolic acids. The flavonoids, alone, represent over 4,000 different compounds that occur ubiquitously in the plant kingdom.
Unlike vitamins, polyphenols are not required for growth and development. Nevertheless, there is strong clinical evidence showing their role in reduction of the risk of chronic disease. Initially considered simple antioxidants, the actions of polyphenols and their metabolites in animal tissues occur through indirect antioxidant protection. Even at minute concentrations in the cell—a strong indication that they are functioning as xenobiotic hormetins—polyphenols can activate endogenous (internal) antioxidant defence systems, modify cellular signalling processes, and inhibit the activities of oxidative and inflammatory molecules.
Polyphenols are involved in the suppression of nuclear factor-kappaB (NF-κΒ), a protein complex that controls transcription of DNA, cytokine* production, and cell survival. NF-κΒ plays a key role in regulating the body’s immune response to infection. The vast majority of serious diseases are rooted in uncontrolled chronic inflammation resulting from dysregulation of the body’s immune response cascade. So, by being able to turn down the actions of NF-κΒ, the body’s inflammation thermostat, polyphenols play an important role in long-term health and disease mitigation.
Through their ability to modulate gene expression by up-regulating the key molecular trigger for cellular redox balance (Nrf2) and down-regulating the trigger for inflammation (NF-κΒ), polyphenols play an essential role in reaching one’s genetically determined lifespan. They are, indeed, indispensable to longevity and good health—they are LifeSpan Essentials.
The two healthiest diets in the world are the traditional Mediterranean diet, found in the Italy/Greece/Crete regions, and the Okinawan diet of Japan. Consequently, for this edition of the guide, NutriSearch has selected a very recent population-based study conducted in the Molise region of Italy, which lies in the heart of the Mediterranean. The Molise study (2016) is the first to report a median intake of flavonoids using the most recent harmonized data from the Eurofir BioActive Substances database and the US Department of Agriculture food composition tables.
The recommended daily intake for the flavonoids in our Blended Standard is based on the median flavonoid intake of 269 mg per day found in the Molise study.49 The phenolic acid intake of 134.5 mg per day in our Blended Standard is based on an estimated 2:1 dietary ratio of flavonoids to phenolic acids (flavonoid intake based on the Molise study) as previously reported by Scalbert and Williamson (2000).3 The calculated daily total polyphenol intake of 403.5 mg, based on the Molise study, is in general agreement with previous US-based studies that estimate a total phenolic intake of 336 mg for individuals consuming up to 10 servings of fruits and vegetables per day.50;51
Alpha lipoic acid (ALA) is a cell-signalling nutrient that is a powerful activator of Nrf2.In combination with acetyl-l-carnitine, coenzyme Q10, and melatonin, ALA demonstrates activation of antioxidant gene expression, up-regulation of energy metabolism and mitochondrial biogenesis, and the maintenance of the structural integrity of the mitochondria.53 As well, a 2013 human cell-culture study demonstrated that ALA increased the expression of the genes encoding detoxification processes in cells exposed to paraquat toxicity (paraquat is a poisonous herbicide that is linked to Parkinson’s disease).
The steroid hormone vitamin D exerts extensive control over gene expression, modulating over 2,000 genes in the human genome. In this regard, it plays an integral role in the regulation of the antioxidant status (redox balance) of the cell. There is increasing evidence that a deficiency in vitamin D contributes to many human diseases, such as Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, hypertension, and cardiovascular disease. Many of the major diseases in humans linked to vitamin D deficiency are associated with dysregulation in both cellular redox status and calcium signalling.
The ability of the vitamin to maintain healthy cells includes its role in modulating those signalling systems involving redox balance and calcium metabolism.54 There is evidence that vitamin D, working with klotho, a hormone involved with regulation of the aging process, maintains molecular signalling systems that promote growth, development, and the redox status of tissues critical for normal physiology.55 Vitamin D directly regulates Nrf2, the master switch controlling the manufacture of endogenous antioxidants, and the processes of detoxification in the liver.55;56
The cancer preventive activity of vitamin E has been documented in epidemiological studies, but large-scale prevention trials using alpha tocopherol have proved disappointing.57 Consequently, recent studies have begun to focus on the other vitamin E forms (isomers), including gamma tocopherol, delta tocopherol and the tocotrienols. These studies provide strong evidence that gamma tocopherol, the principal form of vitamin E in the diet,58 and delta tocopherol, modulate Nrf2 and NF-κΒ signalling pathways more effectively than alpha tocopherol, the principal form of vitamin E found in supplements.59 As well, gamma tocotrienol has been found to block NF-κΒ levels and enhance Nrf2 levels to a greater extent than alpha tocopherol.60
n-Acetylcysteine (NAC), a derivative of the naturally occurring amino acid cysteine (amino acids are the building blocks of proteins) is a potent activator of Nrf2.61-65 Conversely, NAC suppresses NF-κΒ and attenuates the body’s inflammatory cascade.66;67 Through this dual role NAC, like many other cell-signalling nutrients, regulates the expression of a wide array of genes responsible for the overall health of the cell. Supplementation with NAC consequently exerts favourable effects on vascular health, muscle strength, cell-mediated immunity, bone density, prevention of cognitive dysfunction, and the mitigation of nerve degeneration.68
Sulforaphane, a sulfur-containing compound found in broccoli, cauliflower, and other cruciferous vegetables, has been intensely studied as a potent inducer of Nrf2. Its lipophilic (fat-loving) nature and low molecular weight provide sulforaphane with higher bioavailability than the phenol-based nutrients that also activate Nrf2. Compared to the polyphenols curcumin, silibinin, and resveratrol, sulforaphane has been found to more potently activate Nrf2, causing strong up-regulation of endogenous antioxidant enzymes and inducing the process of autophagy.
This criterion examines the polyphenol family of nutrients, notably the bioflavonoids and phenolic acids, as well as alpha lipoic acid, vitamin D, vitamin E (gamma tocopherol and the mixed tocopherols/tocotrienols), n-acetylcysteine, and sulforaphane.
Does the product contain a variety of flavonoids (which may include citrus and other flavonoids, bilberry and related extracts, hesperidin, quercetin, quercitrin, rutin, soy isoflavones, silibinin [silymarin], green tea leaf and green tea extracts, related milk thistle extracts, and procyanidolic oligomers) and related compounds (which may include grape seed and grape seed extract, hawthorn berry and hawthorn extract, pine bark and pine bark extract, pycnogenol, and resveratrol) at a combined potency for this nutrient class recently established in the Blended Standard?
AND does the product contain phenolic acids and related compounds (which may include cinnamon bark and cinnamon bark extract, cranberry and cranberry extract, curcumin and turmeric rhizome, fenugreek, ginger and gingerols, olive fruit and olive extracts, papaya, pomegranate fruit and pomegranate extract, and rosemary), at a combined potency for this nutrient class recently established in the Blended Standard?
AND does the product also contain alpha lipoic acid, vitamin D, vitamin E (gamma tocopherol and the mixed tocopherols/tocotrienols), n-acetylcysteine, and sulforaphane at potencies for these nutrients recently established in the Blended Standard?
For further information on this criterion and evidence of suggested daily intakes, please read Appendix II, available online at www.nutrisearch.ca.
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