#46 - Chris Masterjohn, Ph.D.: Navigating the many pathways to health and disease - NAD and sirtuins, methylation, MTHFR and COMT, choline deficiency and NAFLD, TMAO, creatine, and more

1. Increase Choline for Fatty Liver

Consume enough choline (or precursors like methionine/protein) to clear triglycerides from the liver, as this has been shown in animal studies to prevent or resolve fatty liver disease regardless of the cause.

2. Aim for 1200mg Choline Daily

Strive for approximately 1200 milligrams of choline daily, which can be challenging to achieve through diet alone (e.g., one egg contains ~130mg), to support liver health and prevent fatty liver.

3. Prioritize Food-Based Choline

Opt for phosphatidylcholine from food sources (like eggs and liver) over choline salts in supplements, as it is better absorbed and less likely to generate TMAO in the gut.

4. Increase Choline for MTHFR

Individuals with MTHFR gene variants that reduce methylfolate activity may have a higher choline requirement (e.g., 900-1200mg daily) because they use more choline to compensate for methylation, impacting various bodily functions.

5. Supplement Creatine to Reduce Methyl Demand

Supplementing with creatine (e.g., 5 grams daily) can significantly reduce the body’s overall methyl group demand, as creatine synthesis accounts for a large portion (45%) of methyl group utilization, which can be beneficial for those with compromised methylation capacity.

6. Take Creatine Daily

If supplementing with creatine, take 5 grams daily, regardless of exercise schedule, to maintain steady body stores and support various physiological functions beyond just exercise performance.

7. Optimize Riboflavin for MTHFR

If you have MTHFR gene variants, ensure optimal riboflavin (Vitamin B2) status, as MTHFR is a riboflavin-dependent enzyme and a lower affinity for riboflavin can reduce its activity.

8. Increase Glycine Intake

If you have low methylfolate levels, consider increasing glycine intake (e.g., through bone broth, collagen, gelatin, or glycine powder) as your body may be losing glycine in the urine due to perceived methyl abundance.

9. Glycine for Sleep and Blood Sugar

To potentially improve sleep, take 3 to 6 grams of glycine powder before bed; for better blood sugar control, take 3 to 5 grams of glycine powder with a meal.

10. Use TMG for Methylation Support

If you have difficulty lowering homocysteine despite other interventions, supplementing with trimethylglycine (TMG) can be highly effective, as it supports the choline-dependent pathway for remethylating homocysteine back to methionine.

11. Consider B6 for High Homocysteine

If you have high homocysteine levels that respond to B6 supplementation, it suggests a need for more B6 to support the breakdown of homocysteine, particularly in the fed state.

12. Oral NR for NAD Increase

If aiming to increase NAD levels, oral nicotinamide riboside (NR) may be a superior precursor to nicotinamide, as NR is less prone to immediate detoxification in the liver and more effectively increases hepatic NAD.

13. Consider Methyl Donors with NR

If supplementing with high doses of nicotinamide riboside (NR), consider supplementing with a methyl donor like trimethylglycine (TMG) to counteract the potential depletion of your body’s methyl group supply due to the detoxification of excess nicotinamide.

14. Space Out Choline Intake

When consuming choline-rich foods like eggs, consider spacing out your intake throughout the day rather than eating a large quantity at one sitting, due to a potential absorption cap that could lead to TMAO generation.

15. Eat Eggs for Choline

Consume eggs as a primary source of choline, as they provide choline in a form that is less likely to generate high levels of TMAO in the blood compared to choline tartrate supplements.

16. Limit PUFAs with Fatty Liver

If you have fatty liver (steatosis), be cautious with a high intake of polyunsaturated fatty acids (PUFAs), as they increase vulnerability to progression to steatohepatitis due to more oxidative targets.

17. Avoid Oral NMN Supplements

Oral nicotinamide mononucleotide (NMN) supplements are likely not absorbed intact due to their charged phosphate group, suggesting they may be less effective than NR or other precursors for increasing NAD.

18. Avoid IV NAD Infusions

Intravenous NAD infusions are not recommended as a physiological means of increasing intracellular NAD, and may trigger an inflammatory response or amplify negative signaling.

19. Start Low with NR Supplementation

If experimenting with nicotinamide riboside (NR) supplementation, consider starting with lower doses (e.g., 75mg twice daily) than typically found in commercial products, as a cautious approach to assess individual response.

20. Gelatin for Tendon Health

To increase collagen synthesis in tendons, consider consuming 15 grams of gelatin with a little vitamin C before exercise, as the increased blood flow during activity can help deliver collagen peptides to connective tissues.

21. Optimize Methyl Donors for COMT

Understand that your COMT genotype influences your potential rate of dopamine methylation, but nutritional intake of methyl donors directly impacts actual methylation, suggesting that optimizing these nutrients can influence mental flexibility or stability.

22. Distinguish Concentration from Flux

When interpreting scientific data, especially blood tests or metabolic markers, remember that a static concentration measurement does not fully represent the dynamic ‘flux’ (movement and turnover) of a molecule, which can lead to misinterpretations.

23. Evaluate Evidence for Action

When making health decisions, consider the level of evidence required to take a specific action, but also critically evaluate the level of evidence (or lack thereof) needed to justify inaction or maintaining the status quo.

24. Study Historical Scientific Foundations

To gain a fresher perspective and uncover overlooked details in scientific understanding, delve into the historical foundations and origins of ideas, rather than solely focusing on the latest research.

25. Respect Conventional Science

Avoid dismissing conventional scientific beliefs or established guidelines outright, as understanding their core rationale is crucial, even when exploring progressive or alternative health approaches.

26. Diversify Undergraduate Studies

When planning for graduate school (e.g., medical school), consider studying a completely different subject in undergraduate to gain a fresh perspective and enthusiasm for your chosen graduate field.

27. Leverage Positive Placebo Effects

If a health intervention makes you feel great, even if it’s potentially a placebo effect, leverage that positive feeling, but also be prepared to stop if an intervention makes you feel unwell, regardless of its purported benefits.

28. Prioritize Objective Biochemical Proxies

When self-experimenting with health compounds, prioritize interventions that can be evaluated with objective biochemical proxies rather than solely relying on subjective feelings, as the latter can be influenced by the placebo effect.