Secrets of delaying aging and living disease free Part 1

Secrets of delaying aging and living disease free Part 1 Roman Pawlak, Ph.D, RD www.drromanpawlak.com

Aging results in profound changes that effect all systems, organs and tissues. Pawlak R. Forever young.

Effect of age-related gastric secretions Secretion of smaller amounts of HCL Secretion of weaker HCL Secretion of smaller amounts of pepsinogen Lower conversion of pepsinogen to pepsin Secretion of smaller amounts or even no intrinsic factor

Effect of age-related gastric secretions B12 in food is bound to protein It needs HCL and enzymes for digestion The stomach must make IF, B12 binds to IF Oh & Brown, American Family Physician, March 1, 2003 ; 67(5):979-986

Malabsorption/inadequate intake Serum B12 depletion/deficiency/low (inadequate) concentration Inadequate concentration of B12 in cells/brain/milk

What results from inadequate B12 status?

Plasma Homocysteine (µmol/l) Plasma total homocysteine status of vegetarians compared with omnivores: a systematic review and meta-analysis Obersby et al, Br J Nutr, 2013;109:785-794 Serum vitamin B12 (pmol/l)

Hcy status among Seventh-day Adventists

We have shown that risk for coronary artery disease is represented by a continuum of total homocysteine concentration, with substantial risk Haddad E. Lecture presentation. 6 th International Congress on Vegetarian Nutrition, Loma Linda University, Feb. 26, 2013 occurring between 10 and 15 µmol/l. Jacobsen DW. Clin Chem. 1998;44(8(B)):1833 1843.

B12 and Hcy status among vegans, vegetarians and non-vegetarians

Obersby et al, Br J Nutr, 2013;109:785-794

What health conditions is elevated Hcy associated with?

Role of homocysteine in aortic calcification and osteogenic cell differentiation Van Campenhout A., et al. Atherosclerosis. 2009;202(2): 557 566 The epidemiology data linking Hcy with atherosclerosis is strong ( ). Experimentally Hcy stimulates a range of potentially proatherosclerotic changes, including inflammation and thrombosis and causes apoptosis of endothelial cells.

https://www.washingtonpost.com/apps/g/page/world/deadly-ebola-virus-on-themove-in-africa/904/ Endothelial cells constitute the inner lining of blood vessels

homocysteine smooth muscle cells Damage to or death of the andothelial cells begins the atherosclerotic process Macrophages transformed into foal cells Lipids, calcium, cellular debris Fibrous cap

Humphrey et al, Mayo Clin Proc. 2008;83(11):1203-1212 Each increase of 5 μmol/l in homocysteine level increases the risk of CHD events by approximately 20%, independently of traditional CHD risk factors.

Conclusions Aging is associated with vitamin B12 deficiency and hyperhomocysteinemia Vegetarians, especially vegan, have inadequate serum B12 and elevated Hcy concentration Elevated homocysteine is associated with increased risk of Cardiovascular disease

Secrets of delaying aging and living disease free Part 2 Roman Pawlak, Ph.D, RD www.drromanpawlak.com

Malabsorption/inadequate intake Serum B12 depletion/deficiency/low (inadequate) concentration Inadequate concentration of B12 in cells/brain/milk Elevated homocysteine concentration

Is Vitamin B12 Deficiency a Risk Factor for Cardiovascular Disease in Vegetarians? Pawlak R. Am J Prev Med 2015;48(6):e11 e26 vegetarians with low vitamin B12 status are predisposed to developing circulatory health problems regardless of their favorable profile of traditional heart disease risk factors.

What other health conditions are elevated homocysteine and/or inadequate B12 associated with?

Osteoporosis

Homocysteine Level and the Risk of Osteoporotic Fracture Joyce et al, N Engl J Med, 2004;May 13;350(20):2042-2049 2.5 2 1.5 1 0.5 0 N = 2406, 55 years or older 100% Lowest thcy Highest thcy An increased homocysteine level appears to be a strong and independent risk factor for osteoporotic fractures in older men and women.

Vitamin B12 Levels of Cerebrospinal Fluid in Patients with Organic Mental Disorder van Tiggelen et al. J Orthomolec Psych. 1983; 12(4):305-311 Group 1 N = 23; age 60-85 6 patients with alcohol related brain damage 5 patients with multi-infarct-dementia or Parkinson-related dementia. 12 patients with senile dementia (Alzheimer Type) Group 2 N = 16; age 30-60 organic affective syndrome Group 3 N = 10; age 25-40 Post-natal depression Group 4 N = 10, controls

Vitamin B12 Levels of Cerebrospinal Fluid in Patients with Organic Mental Disorder van Tiggelen et al. J Orthomolec Psych. 1983; 12(4):305-311 Of our total number of 49 patients with organic mental disorder only 4 patients would have been detected with determination of vitamin B12 levels in serum, whilst in fact 30 of these 49 patients have a pathologically low level of vitamin B12 in CSF (cerebrospinal fluid RP) and could be treated effectively with parenteral vitamin B12 as has been demonstrated.

Vitamin B12 Levels of Cerebrospinal Fluid in Patients with Organic Mental Disorder van Tiggelen et al. J Orthomolec Psych. 1983; 12(4):305-311 ( ) it is furthermore suggested that a considerable number of patients is classified and treated as dysthymic disorder (DSM-111) in psychiatric institutions and by psychiatric methods of expensive psycho-social therapy,

Vitamin B12 Levels of Cerebrospinal Fluid in Patients with Organic Mental Disorder van Tiggelen et al. J Orthomolec Psych. 1983; 12(4):305-311 whereas in fact these patients are suffering from an undetected organic affective syndrome, to which cerebral B12 deficiency is at least a contributing, if not a causative factor. In this respect we mention the post-natal depression and the possibly toxic neurasthenic depression.

Cognitive decline

Homocysteine-Lowering by B Vitamins Slows the Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial. Smith et al., PLoS ONE 5(9): e12244 Randomized controlled study N = 271 individuals over 70 years with mild cognitive impairment Group 1 folic acid (0.8 mg/d), vitamin B12 (0.5 mg/d) i vitamin B6 (20 mg/d) Grupa 2 placebo

Homocysteine-Lowering by B Vitamins Slows the Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial. Smith et al., PLoS ONE 5(9): e12244 2.5/0.46 = 5.4 (A) Subtraction image of female participant in the placebo group, age 79 years, with baseline thcy of 22 µmol/l, whose thcy concentration increased by 8 µmol/l over two years. Atrophy rate was 2.50% per year. Atrophy most strongly appears here as enlargement of the ventricles. (B) Subtraction image of female participant in active treatment group, age 72 years, with baseline thcy of 24 µmol/l at baseline, whose thcy concentration decreased by 12 µmol/l over two years. Atrophy rate 0.46% per year. There is no clear visible pattern of atrophy.

Conclusions Inadequate serum vitamin B12 and/or elevated homocysteine concentration are associated with Osteoporotic fractures Depression Cognitive decline/dementia/ Alzheimer s disease

Practical considerations Vitamin B12 supplements are recommended for anyone 50 years and over Vegetarians, especially vegans, should be using vitamin B12 supplements The dose of vitamin B12 supplement is agedependent 100-500 µg/day should be sufficient to maintain adequate serum B12 concentration

Secrets of delaying aging and living disease free Part 3 Roman Pawlak, Ph.D, RD www.drromanpawlak.com

Aging results in profound changes that effect all systems, organs and tissues. Pawlak R. Forever young.

A man is as old as his arteries Vascular aging Decreased nitric oxide synthesis Increased production of reactive oxygen species (ROS) Increased platelet aggregation effect Increased stiffness and thickness of arteries Increased vascular inflammation and atherogenesis Increased systolic and diastolic BP Increased risk of heart attack and stroke Shinmura K. Geriatr Gerontol Int 2011;11:143 156.

Can anything be done to reverse or at least slow down the process?

Vascular aging EPA & DHA Decreased nitric oxide synthesis Increased nitric oxide synthesis Increased production of reactive oxygen species (ROS) Increased stiffness and thickness of arteries Increased platelet aggregation effect Increased vascular inflammation and atherogenesis Increased production of superoxide dismutase Decreased stiffness and thickness of arteries Platelet anti-aggregation effect Decreased vascular inflammation and atherogenesis Increased systolic and diastolic BP Decreased systolic and diastolic BP

Fatty acids Saturated fatty acids: lauric, myristic, palmitic, stearic acid Monounstaturated fatty acids: Oleic acid Polyunsaturated fatty acids: Omega-3 (n-3): alpha-linolenic acid, EPA & DHA Omega-6 (n-6): lenoleic acid, arachidonic acid

Conclusions and recommendations from the symposium, Beyond Cholesterol: Prevention and Treatment of Coronary Heart Disease with n 3 Fatty Acids Deckelbaum et al. Am J Clin Nutr 2008;87(suppl):2010S 2S. Current knowledge for which a general consensus exists Consistent evidence indicates that n-3 fatty acids contribute substantially to lowering coronary heart disease (CHD) mortality risk attributable to reduced arrhythmic death in the primary prevention setting and after an initial cardiac event (secondary prevention).

Vegetarians dietary patterns and mortality in Adventist Health Study 2 Orlich et al. JAMA Intern Med. 2013;173(13): 1230 1238 All cause IHD CVD Other Non-veg. Ref. Ref. Ref. Ref. Semi-veg. -8% -8% -15% -1% Pesco-veg. -19% -35% -20% -29% LOV -9% -18% -10% -9% Vegans -15% -8% -9% -26%

Beyond cardiovascular health effects of EPA & DHA

Omega-3 polyunsaturated fatty acid supplements and cognitive decline: Singapore Longitudinal Aging Studies Gao et al. J Nutr Health Aging, 2011;15(1):32-35. N = 1,475 Chinese adults aged 55 years Daily n-3 PUFA supplements intake was significantly (p=0.024) associated with lower risk of cognitive decline (OR=0.37, 95% C.I. 0.16-0.87) after controlling for age, gender, education, number of medical comorbidity, the presence of vascular risk factors/diseases, smoking, alcohol drinking, depression, APOE e4 allele carrier status, nutritional status, level of leisure activities, baseline MMSE and length of follow-up.

Intakes of fish and polyunsaturated fatty acids and mild-tosevere cognitive impairment risks: a dose-response metaanalysis of 21 cohort studies Zhang et al., Am J Clin Nutr 2016;103:330 340 0.1-g/d increment of dietary docosahexaenoic acid (DHA) intake was associated with lower risks of dementia (RR: 0.86; 95% CI: 0.76, 0.96; P, 0.001, I 2 = 92.7%) and AD (RR: 0.63; 95% CI: 0.51, 0.76; P, 0.001, I 2 = 94.5%).»

Practical applications