4 replies to this topic

[Uncle Frank]

Aging: Clinical trial on potential reversal of epigenetic age using a diet and lifestyle

https://www.scienced...10527145324.htm

 

A randomized controlled clinical trial was conducted among 43 healthy adult males between the ages of 50-72. The 8-week treatment program included diet, sleep, exercise and relaxation guidance, and supplemental probiotics and phytonutrients.

 

[ta5]

Aging (Albany NY). 2021 Apr 12;13(7):9419-9432. doi: 10.18632/aging.202913. Epub 2021 Apr 12.

Potential reversal of epigenetic age using a diet and lifestyle intervention: a pilot randomized clinical trial.

Fitzgerald KN, Hodges R, Hanes D, et al.

PMID: 33844651

 

"The dietary recommendations employed as part of the treatment protocol for this study were based largely on biochemistry and generalized measures of health, because few dietary associations with the DNAmAge clock have yet been established. A modest, but significant, reduction in DNAmAge in individuals consuming a non-specific lean meat, fish and plant-based diet (as measured by blood carotenoids) has been observed [12]. It is possible that changes of a greater magnitude require a more targeted approach. The dietary intervention used here was also plant-centered, but including a high intake of nutrients that are substrates or cofactors in methylation biosynthetic pathways (e.g. containing folate, betaine), ten-eleven translocation (TET) demethylase cofactors and modulators (e.g. alpha ketoglutarate, vitamin C and vitamin A) [13] and polyphenolic modulators of DNA methyl transferases (DNMT) (e.g. curcumin, epigallocatechin gallate (EGCG), rosmarinic acid, quercetin, luteolin) [14]. It also included limited nutrient-dense animal proteins (e.g. liver, egg). The diet restricted carbohydrates and included mild intermittent fasting, both designed to lower glycemic cycling. The diet was supplemented daily with a fruit and vegetable powder, also rich in polyphenolic modulators of DNMT activity, and a probiotic providing 40 million CFU of Lactobacillus plantarum 299v. L. plantarum has been shown to be a folate producer in the presence of para aminobenzoic acid (PABA) [15]; it also has been demonstrated to alter gene expression [16]."

 

 

Summary of dietary and lifestyle interventions*

 

Dietary Prescription

 

Guidance per week:

3 servings of liver

•(1 serving = 3 oz)

•Preferably organic

5-10 eggs

•Ideally free-range, organic, omega-3 enriched

Guidance per day:

2 cups of dark leafy greens

•Measured raw, chopped, and packed

•Including kale, Swiss chard, collards, spinach, dandelion, mustard greens

•Does not include salad greens such as romaine, iceberg, Spring mix

2 cups cruciferous vegetables

•Measured raw, chopped, and packed

•Includes broccoli, cabbage, cauliflower, Brussels sprouts, bok choy, arugula, kale, mustard greens, watercress, rutabaga, kohlrabi, radish, Swiss chard, turnip

3 additional cups colorful vegetables of your choosing (excluding white potatoes, sweetcorn)

1-2 medium beet

4 tbsp (1/4 cup) pumpkin seeds (or pumpkin seed butter)

4 tbsp (1/4 cup) sunflower seeds (or sunflower seed butter)

1+ serving methylation adaptogens, choose from:

•1/2 cup berries (wild preferred)

•1/2 tsp rosemary

•1/2 tsp turmeric

•2 medium cloves garlic

•2 cups green tea (brewed 10 minutes)

•3 cups oolong tea (brewed 10 minutes)

6 oz animal protein

•Grass-fed, pastured, organic and hormone/antibiotic-free

2 servings of low glycemic fruit

General guidance:

Organic preferred over conventional

Stay hydrated

Don’t eat between 7pm and 7am

Include “healthy” oils

•Balance types of fat

•E.g. coconut, olive, flaxseed and pumpkin seed oil

Avoid added sugar/candy, dairy, grains, legumes/beans

Minimize plastic food containers

 

Supplement Prescription

 

PhytoGanix®, a combination of organic vegetables, fruits, seeds, herbs, plant enzymes, prebiotics and probiotics at a dose of 2 servings daily, divided

UltraFlora® Intensive Care, containing Lactobacillus plantarum 299v at a dose of 2 capsules daily, divided

 

Exercise Prescription

 

Minimum of 30 minutes of exercise per day for at least 5 days per week, at an intensity of 60-80% of maximum perceived exertion

 

Sleep Prescription

 

Average a minimum of 7 hours of sleep per night

 

Stress Management Prescription

 

Breathing exercise Steps to Elicit the Relaxation Response developed by Herbert Benson MD, twice daily

 

 

* Patent pending.

 

Edited by ta5, 28 May 2021 - 08:30 PM.

[albedo]

Great finding, thanks ! I also took note of the concerning recap on folates in particular, from supplementation, in relatively high dose and risk of cancer:

 

"...In designing the present study, extra-dietary supplementation of methyl donor nutrients was specifically avoided because a growing body of epidemiological evidence indicates potential long-term risks, to which the short-term studies were not sensitive. Although overall data are mixed, and certain conditions (e.g. pregnancy, macrocytic anemia, hyper-homocysteinemia, dietary limitations) often require extra-dietary supplementation, several trials have found a positive association between methyl donor supplementation and increased cancer risk: Published long-term follow up on 2,524 participants in the B-PROOF trial which assessed the effect of 2-3 years of daily supplementation with 400 mcg folic acid and 500 mcg vitamin B12 found an increased risk of overall cancer (HR 1.25, 95% CI 1.00-1.53), p=0.05) and colorectal cancer in particular (HR 1.77, 95% CI 1.08-2.90, p=0.02) [38]. A meta-analysis of 2 trials in Norway similarly reported that 800 mcg folic acid plus 400 mg vitamin B12 daily was associated with increased cancer outcomes and all-cause mortality [39]. In contrast, dietary folate intake from food was found to be inversely associated with non-muscle-invasive bladder cancer progression in a study that also found higher recurrence for folic acid intake [40], and baseline dietary folate intake was inversely associated with prostate cancer risk in a trial that subsequently identified an increased risk of prostate cancer in the treatment arm that received 1 mg folic acid per day for 10 years [41]. Also relevant is the demonstration, albeit in a small study, adding dietary supplements of folic acid, vitamin B6 and vitamin B12 to a vitamin D plus calcium intervention increased biological aging (sex-adjusted odds ratio 5.26 vs vitamin D plus calcium alone) during a 1-year intervention [42]..."

[ta5]

The risks were from folic acid in each reference. The risks of folic acid has been discussed on LongeCity before. 

Edited by ta5, 29 May 2021 - 06:12 PM.

[pamojja]

 A meta-analysis of 2 trials in Norway similarly reported that 800 mcg folic acid plus 400 mg vitamin B12 daily was associated with increased cancer outcomes and all-cause mortality [39].

 

Makes me chuckle about having beaten the grim ripper. Between a severe PAD, a mild COPD and a silent stroke during the last 12 years, theoretical 5-year mortality would have easily added up to 100%. Instead experienced only remissions.

 

Think neccesary co-factors, like life-style changes and comprehensive supplementation, really need to be in place too, for experiencing remissions instead of dying. Despite the 2 mg of folates or B12s I took ever day for the last 12.
 

Edited by pamojja, 30 May 2021 - 11:10 AM.