Protocol development in integrative medicine is not typically a simple process. Individuals require individualized care, and what works for one patient may not work for another.
To establish these protocols, we first developed a Rating Scale that could be used to discern the rigor of evidence supporting a specific nutrient’s therapeutic effect.
The following protocols were developed using only A through C-quality evidence.
The biomarkers of oxidative stress have been strongly linked to aging. (26)(29) Oxidative stress biomarkers, such as lipoprotein phospholipase A2 (Lp-PLA2), isoprostanes, malondialdehyde (MDA), 8-hydroxy-2-deoxyguanosine (8-Oxo-dG), derivatives of reactive oxygen metabolites, oxidized glutathione/glutathione, 4-hydroxy-2, 3-nonenal (4-HNE), and protein carbonylation, have all been linked with increased risk of frailty and pre-frailty. (29) In addition, cardiovascular mortality has been associated with increased serum markers of oxidative stress, such as derivatives of reactive oxygen metabolites (D-ROM) and total thiol levels (TTL). (26)
Antioxidants may help to mitigate the potential negative effects of prolonged oxidative stress. Additionally, ingredients with antioxidant function have shown potential for reducing oxidative damage caused by exercise when taken by healthy individuals.
The protocol below is intended to support healthy aging through ingredients focused on attenuating damage caused by oxidative stress.
Coenzyme Q10 (CoQ10)
200 mg, once per day, minimum 2 weeks (25)
- Superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were increased, and malondialdehyde (MDA) and diene levels were decreased after CoQ10 supplementation (33, 15, 12)
- CoQ10 supplementation has been shown to decrease the level of age-related cardiovascular fibrosis through its antioxidant and anti-inflammatory actions (7, 8)
- Systematic review and meta-analysis of 19 studies found CoQ10 supplementation to improve markers for oxidative stress demonstrated by and increase in total antioxidant capacity (TAC), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT), and decrease in malondialdehyde (MDA) (23)
- Two systematic reviews have shown improvements in antioxidant systems as demonstrated by increases in SOD, CAT, and TAC activity, and decreases in MDA and diene levels (1, 12)
- When given 200 mg of ubiquinol before strenuous exercise, healthy adults were found to have decreased oxidative stress and increased antioxidant status as demonstrated by improved levels of isoprostanes, 8-OHdG, oxidized LDL, hydroperoxides and CAT activity (25)
600-2000 mg, once per day, minimum 12 weeks (24)
- Curcumin (in a Longvida® proprietary preparation) supplementation has been shown to increase vascular nitric oxide bioavailability, reduce oxidative stress, and, therefore, improve artery endothelial resistance (24)
- Meta-analysis of 8 clinical studies found curcumin supplementation improved oxidative stress demonstrated by decreases in MDA when given curcuminoids at a dose of 600 mg per day; additionally, when piperine was used in combination, the effect was greater (20)
- Systematic review of 11 articles found curcumin effective in decreasing inflammation, oxidative stress, pain, and muscle damage while improving muscle performance and recovery (30)
- Meta-analysis of 8 clinical studies found curcumin supplementation improved oxidative stress demonstrated by a decrease in MDA and increase in SOD when supplemented for four weeks; effects improved when combined with peperine (20)
- Systematic review and meta-analysis of 15 randomized controlled found curcumin improved inflammation and antioxidant status as demonstrated by decreases in interleukin 6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), and MDA (31)
- Polyphenol supplementation in normal dose (299 mg/d) or high dose (745 mg/d) decreased 8-hydroxy-2′-deoxyguanosine (8-Oxo-dG), 8-iso-prostaglandin F2α (8-iso-PGF2α), erythrocyte catalase, and glutathione reductase (GR) activity in obese and overweight non-smoking adults; additionally, waist circumference, BMI, and leptin were decreased (22)
- In different age groups, resveratrol provided protection against protein carbonylation and lipid peroxidation, and cellular levels of glutathione (GSH) and sulfhydryl (-SH) were restored during oxidative injury in erythrocytes; additionally, resveratrol has been shown to up-regulate plasma membrane redox system (PMRS) and ascorbate free radical reductase activity (19)
- Systematic review and meta-analysis of 14 studies found improved antioxidant status and subsequent performance improvements as demonstrated by a 1.9% increase in exercise performance in athletes when supplemented for a minimum of 7 days (28)
- Improved endothelial function was correlated with improvements in antioxidative enzymatic activity and in the oxidative and inflammatory profile (14)
- 5 mg and 15 mg doses of lycopene decreased oxidative stress as shown by decreased lymphocyte DNA comet tail lengths and increased SOD activity; 15 mg doses additionally decreased hs-CRP, systolic blood pressure, sICAM-1 and sVCAM-1 and increased β-carotene, LDL-particle size, and reactive hyperemia peripheral arterial tonometry (RH-PAT) (14)
- Lycopene supplementation at a dose of 30 mg per day decreased oxidative damage to DNA and urinary 8-hydroxy deoxoguanosine (8-OHdG) in healthy volunteers (6)
- Postmenopausal women experienced a decrease in endogenous DNA damage when given 12 mg of single carotenoid (beta-carotene, lutein, or lycopene) of 4 mg of mixed carotenoids (34)
- Older individuals have lower glutathione levels, lower glutathione synthesis, higher oxidative stress and F(2)-isoprostanes but can be improved with supplementation of glutathione precursors including NAC and glycine (27)
- Increased blood catalase, GSH, GSH/GSSG, glutathione peroxidase, neutrophil capacity, and total thiol groups (TTG), and reduced GSSG, oxidized homocysteine (Hcy) and free Hcy:oxidized Hcy ratio, superoxide anions, MDA, NO, VCAM-1, improving antioxidant status and possibly slowing progression of vascular damage (18, 3, 21, 32, 9, 5)
- Reduced total peroxide and oxidative stress indices, malondialdehyde (MDA), sperm DNA damage and increased total antioxidant capacity (2, 11)
- Reduced oxidative stress indices, malondialdehyde (MDA), sperm DNA fragmentation and increased total antioxidant capacity in infertile men with asthenoteratozoospermia (11)
- Reduced protein carbonyl groups, serum lead content, and increased glutamate dehydrogenase activity indicating improved oxidative stress in workers with lead exposure (13)
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