Mendelian randomization studies show that genetically predicted low vitamin D levels are linked to higher all-cause mortality and approximately 25% higher respiratory disease mortality.
"these Mendelian randomization studies have found that people with genetically low vitamin D levels have a higher all-cause mortality. They've got like a 25% higher mortality from respiratory disease." (said at 0:19:05)
A landmark nonlinear Mendelian randomization study of 307,601 UK Biobank participants (Sutherland et al., 2022) found that genetically predicted low 25-hydroxyvitamin D [25-(OH)D] levels were causally linked to increased all-cause mortality, as well as significantly increased mortality from respiratory disease, cardiovascular disease, and cancer. However, the specific 25% increase (odds ratio 1.25, 95% CI 1.16 to 1.35, comparing 25 nmol/L vs 50 nmol/L) was the estimate for all-cause mortality, which the speaker conflated with respiratory disease mortality.
- supports: Vitamin D Deficiency Increases Mortality Risk in the UK Biobank : A Nonlinear Mendelian Ra… (Annals of internal medicine 2022) · cited 131x in the literature
"The association of genetically predicted 25-(OH)D with all-cause mortality was L-shaped ( P for nonlinearity < 0.001), and risk for death decreased steeply with increasing concentrations until 50 nmol/L. Evidence for an association was also seen in analyses of mortality from cancer, CVD, and respiratory diseases ( P ≤ 0.033 for all outcomes). Odds of all-cause mortality in the genetic analysis were estimated to increase by 25% (odds ratio, 1.25 [95% CI, 1.16 to 1.35]) for participants with a measured 25-(OH)D concentration of 25 nmol/L compared with 50 nmol/L." (abstract, results, passage verified)
pubmedfull study (doi)
Estrogen increases the conversion of ALA into EPA and DHA by up to 20%.
"estrogen does dramatically increase that conversion. It makes it up to 20% better." (said at 0:24:45)
Evidence from human stable isotope tracer studies indicates that young women have substantially higher conversion efficiency of alpha-linolenic acid (ALA) into long-chain omega-3 fatty acids compared to men, an effect attributed to estrogen upregulating desaturase enzymes (such as Delta-6 desaturase) and reducing beta-oxidation. In adult men, conversion of ALA to EPA is estimated at approximately 8% and to DHA is <0.1%, whereas in young women fractional conversion of ALA to EPA reaches approximately 21% and conversion to DHA is roughly 9%. The speaker's figure of 'up to 20%' appears to refer to the absolute fractional conversion rate observed in women (~21%) rather than a 20% relative enhancement, though estrogen does significantly facilitate this metabolic pathway.
- context: Conversion of alpha-linolenic acid to longer-chain polyunsaturated fatty acids in human ad… (Reproduction, nutrition, development 2005) · cited 921x in the literature
"The fractional conversion of alphaLNA to the longer chain n-3 PUFA is greater in women which may be due to a regulatory effect of oestrogen. A lower proportion of alphaLNA is used for beta-oxidation in women compared with men." (abstract, results, passage verified)
pubmedfull study (doi) - context: Long-chain n-3 PUFA: plant v. marine sources. (The Proceedings of the Nutrition Society 2006) · cited 359x in the literature
"However, alphaLNA-feeding studies and stable-isotope studies using alphaLNA, which have addressed the question of bioconversion of alphaLNA to EPA and DHA, have concluded that in adult men conversion to EPA is limited (approximately 8%) and conversion to DHA is extremely low (<0.1%). In women fractional conversion to DHA appears to be greater (9%), which may partly be a result of a lower rate of utilisation of alphaLNA for beta-oxidation in women. However, up-regulation of the conversion of EPA to DHA has also been suggested, as a result of the actions of oestrogen on Delta6-desaturase" (abstract, results, passage verified)
pubmedfull study (doi)
Lactate acts as a signaling molecule that activates brain-derived neurotrophic factor (BDNF) at the blood-brain barrier.
"So lactate actually is a signaling molecule. It has been shown to activate brain-derived neurotrophic factor at the blood-brain barrier. It activates it." (said at 0:51:10)
Lactate is recognized as a signaling molecule that promotes brain-derived neurotrophic factor (BDNF) expression; however, published preclinical research indicates that peripheral lactate crosses the blood-brain barrier to stimulate BDNF expression and signaling within brain parenchyma (such as the hippocampus), rather than activating BDNF at the blood-brain barrier itself. In a 2019 mouse study by El Hayek et al., exercise-induced muscle lactate crossed the blood-brain barrier and induced hippocampal Bdnf expression and TRKB signaling via a SIRT1-dependent pathway.