Protein and Amino Protein and Amino AcidsAcids

Leo Galland, M.D., F.A.C.P., Leo Galland, M.D., F.A.C.P., F.A.C.N.F.A.C.N.

Foundation for Integrated Foundation for Integrated MedicineMedicine

How much protein does a person How much protein does a person really need? Does the source of really need? Does the source of

protein matter?protein matter? __________________________________ __________________________________

““Few issues in nutritional science Few issues in nutritional science have aroused such long-standing and have aroused such long-standing and deep-seated controversies as protein deep-seated controversies as protein and amino acid requirements.” and amino acid requirements.”

Millward, J Nutr 1997Millward, J Nutr 1997

The Elements of LifeThe Elements of Life CCarbonarbon OOxygenxygen HHydrogenydrogen NNitrogenitrogen SSulfurulfur PPhosphorushosphorus ““Minerals”: Ca, Mg, Na, K, Fe, Zn, Cu, Se, Minerals”: Ca, Mg, Na, K, Fe, Zn, Cu, Se,

Mn, Cr, Mo, Vn, Ni...Mn, Cr, Mo, Vn, Ni...

Essential Amino AcidsEssential Amino Acids IsoleucineIsoleucine LeucineLeucine LysineLysine Methionine*Methionine* Phenylalanine*Phenylalanine* ThreonineThreonine TryptophanTryptophan Valine Valine Arginine*Arginine* HistidineHistidine

Major Non-essential Amino Major Non-essential Amino AcidsAcids

AlanineAlanine AsparagineAsparagine AspartateAspartate CysteineCysteine GlutamateGlutamate GlutamineGlutamine GlycineGlycine ProlineProline SerineSerine TyrosineTyrosine

The Fate of Dietary The Fate of Dietary ProteinProtein

Digestion and absorption (efficiency Digestion and absorption (efficiency varies by 25%, depending upon varies by 25%, depending upon protein source)protein source)

Maintenance of body protein storesMaintenance of body protein stores Net protein synthesis (less than 10% Net protein synthesis (less than 10%

of minimum requirements, even in of minimum requirements, even in children)children)

Synthesis of non-protein compoundsSynthesis of non-protein compounds Oxidative deamination Oxidative deamination

Essential Non-ProteinEssential Non-Protein Nitrogen-Requiring Nitrogen-Requiring

ProcessesProcesses Nucleic acid synthesis, including adenosine Nucleic acid synthesis, including adenosine

for ATP (glutamate, aspartate, glycine, for ATP (glutamate, aspartate, glycine, glutamine)glutamine)

Nervous system: Nervous system: Neurotransmitter/neuropeptide synthesis Neurotransmitter/neuropeptide synthesis (phenylalanine, tryptophan, glutamate….)(phenylalanine, tryptophan, glutamate….)

Immune system: Cytokine production,Anti-Immune system: Cytokine production,Anti-oxidant protection (taurine; glutathione: oxidant protection (taurine; glutathione: cysteine, glutamate, glycine)cysteine, glutamate, glycine)

Skeletal muscle: Creatine (methionine, Skeletal muscle: Creatine (methionine, arginine, glycine)arginine, glycine)

Cardiovascular system: Nitric oxide synthesis Cardiovascular system: Nitric oxide synthesis (arginine)(arginine)

GI tract: Mucin secretion (threonine, cysteine, GI tract: Mucin secretion (threonine, cysteine, serine, proline)serine, proline)

How dietary protein is How dietary protein is recorded:recorded:

grams/day [50-135]grams/day [50-135]

mg/kg body weight [800-1500]mg/kg body weight [800-1500]

% of kcalories consumed [10-% of kcalories consumed [10-20]20]

Minimum Protein Minimum Protein RequirementsRequirements

Obligatory Nitrogen Loss (metabolic ward)Obligatory Nitrogen Loss (metabolic ward)36 mg/kg/day urinary (85%)36 mg/kg/day urinary (85%)12 mg/kg.day fecal (13%)12 mg/kg.day fecal (13%)8 mg/kg/day sweat, skin, saliva, hair (2%)8 mg/kg/day sweat, skin, saliva, hair (2%)54 mg of nitrogen/kg/day total54 mg of nitrogen/kg/day total

Replacement requires 340 mg Replacement requires 340 mg protein/kg/dayprotein/kg/day 70 kg person: 24 gm/day70 kg person: 24 gm/day

WHO safe minimum: 750 mg/kg/day, of WHO safe minimum: 750 mg/kg/day, of which 84 mg/kg should be essential amino which 84 mg/kg should be essential amino acidsacids 70 kg person = 52 gm/day70 kg person = 52 gm/day 60 kg person = 46 gm/day60 kg person = 46 gm/day

Minimum Safe Protein Minimum Safe Protein Requirements for ChildrenRequirements for Children

Newborns 1.85 mg/kg/dayNewborns 1.85 mg/kg/day Infants: 1.5-1.65 gm/kg/dayInfants: 1.5-1.65 gm/kg/day Toddlers: 1.1-1.2 mg/kg/dayToddlers: 1.1-1.2 mg/kg/day School children: 1.0 mg/kg/daySchool children: 1.0 mg/kg/day Adolescents 0.9-0.95 mg/kg/dayAdolescents 0.9-0.95 mg/kg/day

N-balance depends upon caloric intake. N-balance depends upon caloric intake. Fewer calories increase protein needs. Fewer calories increase protein needs. Profound inter-individual differencesProfound inter-individual differences

US Adult Protein RDA'sUS Adult Protein RDA's

femalefemale male male CaloriesCalories 1900-22001900-2200 2300-29002300-2900

ProteinProtein 46 gm 46 gm 71 71 gmgm

about 10% of caloriesabout 10% of caloriestypical US diet: 15% of caloriestypical US diet: 15% of calories

popular weight loss diets: 30% of caloriespopular weight loss diets: 30% of caloriesexcess protein is oxidized by deaminationexcess protein is oxidized by deamination

       

       

       

       

       

       

                                                                                                          

                                      

Ketogenic Amino AcidsKetogenic Amino Acids Exclusively ketogenic:Exclusively ketogenic:

LeucineLeucineLysineLysine

Ketogenic and glucogenic:Ketogenic and glucogenic:ThreonineThreonineIsoleucineIsoleucinePhenylalaninePhenylalanineTyrosineTyrosineTryptophanTryptophan

Hunter-Gatherer DietsHunter-Gatherer Diets

Compared to typical U.S. diet:Compared to typical U.S. diet:

high dietary protein (19-35% of high dietary protein (19-35% of calories) calories)

relatively low level of dietary relatively low level of dietary carbohydrate (22-40% of calories) carbohydrate (22-40% of calories)

variable fat intake (28-58% of variable fat intake (28-58% of calories) calories)

The paradoxical nature of hunter-gatherer diets: The paradoxical nature of hunter-gatherer diets: meat-based, yet non-atherogenicmeat-based, yet non-atherogenic L Cordain, S B L Cordain, S B

Eaton, et alEaton, et al Eur J Clin NutrEur J Clin Nutr 2002; 56, Suppl 1, S42-S52 2002; 56, Suppl 1, S42-S52 13 known quantitative dietary studies 13 known quantitative dietary studies

of HG demonstrate that animal food of HG demonstrate that animal food provided the dominant (65%) energy provided the dominant (65%) energy source, while gathered plant foods source, while gathered plant foods comprised the remainder (35%).comprised the remainder (35%).

Comprehensive review of 229 HG Comprehensive review of 229 HG societies: mean subsistence societies: mean subsistence dependence upon gathered plant dependence upon gathered plant foods was 32%, whereas it was 68% foods was 32%, whereas it was 68% for animal foods. for animal foods.

Changes in nutritional status and patterns of Changes in nutritional status and patterns of morbidity among free-living elderly persons: a 10-morbidity among free-living elderly persons: a 10-

year study. Vellas et al, Nutr 1997; 13 :515-9year study. Vellas et al, Nutr 1997; 13 :515-9 304 healthy French elderly (median age 304 healthy French elderly (median age

72 in 1980): 97 (34.2%) remained 72 in 1980): 97 (34.2%) remained healthy;74 (26.5%) became frail or sick; healthy;74 (26.5%) became frail or sick; 54 (19.1%) died, 57 (20.1%) dropped 54 (19.1%) died, 57 (20.1%) dropped out. Median protein intake was 0.8-1.2 out. Median protein intake was 0.8-1.2 g/kg of body weight in 1980-81. g/kg of body weight in 1980-81.

Protein intake 1.20-1.76 g/kg Protein intake 1.20-1.76 g/kg associated with fewer health problems associated with fewer health problems over the next 10 years vs protein over the next 10 years vs protein intakes < 0.8 g/kgintakes < 0.8 g/kg

High-protein low fat diets are effective for weight High-protein low fat diets are effective for weight loss and favorably affect biomarkers in healthy loss and favorably affect biomarkers in healthy adults. Johnson et al. J Nutr 2003; 134: 586-91. adults. Johnson et al. J Nutr 2003; 134: 586-91.

20032003;; 20 adults, low fat (<30% kcal) diets, 20 adults, low fat (<30% kcal) diets,

consuming either 10% or 30% proteinconsuming either 10% or 30% protein Weight loss (-6% over 6 weeks) and fat Weight loss (-6% over 6 weeks) and fat

loss (-9 to -11%) not affected by proteinloss (-9 to -11%) not affected by protein Cholesterol (-10 to -12%), insulin (-25%), Cholesterol (-10 to -12%), insulin (-25%),

uric acid (-22 to -30%) similar changesuric acid (-22 to -30%) similar changes Hunger and satiety better with high Hunger and satiety better with high

proteinprotein Ca-balance unaffected, N-balance better Ca-balance unaffected, N-balance better

A Reduced Ratio of Dietary Carbohydrate to Protein Improves A Reduced Ratio of Dietary Carbohydrate to Protein Improves Body Composition and Blood Lipid Profiles during Weight Body Composition and Blood Lipid Profiles during Weight

Loss in Adult Women. Layman DK. J.Nutr. 2003; 133:411-417Loss in Adult Women. Layman DK. J.Nutr. 2003; 133:411-417 24 women age 45 to 56, BMI >26 kg/m2 24 women age 45 to 56, BMI >26 kg/m2 Isocaloric, matched-fat diets, 68 vs 125 g protein/day Isocaloric, matched-fat diets, 68 vs 125 g protein/day

for 10 weeks. for 10 weeks. HP loss of fat/lean (6.3 ± 1.2 g/g) vs LP (3.8 ± 0.9).HP loss of fat/lean (6.3 ± 1.2 g/g) vs LP (3.8 ± 0.9). Cholesterol down 10 for both, TGs down only for HP Cholesterol down 10 for both, TGs down only for HP

(21%) (21%) LP had higher insulin responses to meals and LP had higher insulin responses to meals and

postprandial hypoglycemiapostprandial hypoglycemia HP reported greater satiety. HP reported greater satiety. Increasing the proportion of protein to CHO in the Increasing the proportion of protein to CHO in the

diet of adult women has positive effects on body diet of adult women has positive effects on body composition, blood lipids, glucose homeostasis and composition, blood lipids, glucose homeostasis and satiety during weight loss.satiety during weight loss.

Randomized trial on protein vs carbohydrate in ad Randomized trial on protein vs carbohydrate in ad libitum fat reduced diet for the treatment of libitum fat reduced diet for the treatment of

obesity. Skov et al. Int J Obes 1999; 50:418-30obesity. Skov et al. Int J Obes 1999; 50:418-30

50 subjects, protein of 12% vs 25% of 50 subjects, protein of 12% vs 25% of kcal, mean BMI of 30.8 and 30.0.kcal, mean BMI of 30.8 and 30.0.

27 week weight loss: high protein 8.9 27 week weight loss: high protein 8.9 kg, high CHO 5.1 kgkg, high CHO 5.1 kg

27 week fat loss: high protein 7.6 kg, 27 week fat loss: high protein 7.6 kg, high CHO 4.3 kg (84-85% of total high CHO 4.3 kg (84-85% of total weight loss)weight loss)

Kcal consumed: 2139 high protein vs Kcal consumed: 2139 high protein vs 2605 high CHO.2605 high CHO.

Dietary protein and risk of ischemic heart disease Dietary protein and risk of ischemic heart disease in women. Hu et al, Amer J Clin Nutr, 1999. 70: in women. Hu et al, Amer J Clin Nutr, 1999. 70:

221-7221-7

80,082 women aged 34–59 y 80,082 women aged 34–59 y Median protein 14.7% of kcal to 24.0% of kcal by Median protein 14.7% of kcal to 24.0% of kcal by

quintile. Higher protein associated with less tobacco quintile. Higher protein associated with less tobacco and alcohol use, more exercise and multivitamin and and alcohol use, more exercise and multivitamin and vit E supplements, more fat, saturated fat, vit E supplements, more fat, saturated fat, cholesterol, folate, meat, dark bread, fruits and cholesterol, folate, meat, dark bread, fruits and vegetables, and less carbohydrate (white bread, vegetables, and less carbohydrate (white bread, potatoes, sweets and desserts.)potatoes, sweets and desserts.)

High protein intakes reduced risk of ischemic heart High protein intakes reduced risk of ischemic heart disease: RR 0.74 (95%). Both animal and vegetable disease: RR 0.74 (95%). Both animal and vegetable protein contributed to the lower risk, but most of the protein contributed to the lower risk, but most of the protein came from animal sources. This inverse protein came from animal sources. This inverse association was similar in women with low- or high-association was similar in women with low- or high-fat diets.fat diets.

Conclusion: Increased dietary protein does not Conclusion: Increased dietary protein does not increase and may reduce risk of ischemic heart increase and may reduce risk of ischemic heart disease.disease.

Short-term effects of substituting protein for carbohydrate in Short-term effects of substituting protein for carbohydrate in the diets of moderately hypercholesterolemic human the diets of moderately hypercholesterolemic human

subjects. Wolfe BM, Giovannetti PM.subjects. Wolfe BM, Giovannetti PM. Metabolism 1991 Metabolism 1991 Apr;40(4):338-43.Apr;40(4):338-43.

Hypercholesterolemic human subjects Hypercholesterolemic human subjects (four men, six women) (four men, six women)

Diets: 23% v 11% of energy as protein, Diets: 23% v 11% of energy as protein, 24% as fat, 53% v 65% as carbohydrate. 24% as fat, 53% v 65% as carbohydrate. Isocaloric substitution of protein for Isocaloric substitution of protein for CHO during low fat dietCHO during low fat diet

High protein: HDL-C higher by 12% High protein: HDL-C higher by 12% (p<.01), total cholesterol (TC) lower by (p<.01), total cholesterol (TC) lower by 6.5% (p< .001), LDL-C lower by 6.4% 6.5% (p< .001), LDL-C lower by 6.4% (p<.02), TG lower by 23% (p<.02). LDL-(p<.02), TG lower by 23% (p<.02). LDL-C/HDL-C lower by 17% (p<.001C/HDL-C lower by 17% (p<.001). ).

Cardiovascular Disease and Diabetes: Inverse relationship between Cardiovascular Disease and Diabetes: Inverse relationship between urinary markers of animal protein intake and urinary markers of animal protein intake and

blood pressure in Chinese: results from the WHO Cardiovascular blood pressure in Chinese: results from the WHO Cardiovascular Diseases and Alimentary Comparison (CARDIAC) Study.Diseases and Alimentary Comparison (CARDIAC) Study.

Liua L et al,Liua L et al, Int J Epidemiology 2002;31:227-233Int J Epidemiology 2002;31:227-233 Urinary 3-methylhistidine (3MH) excretion (a Urinary 3-methylhistidine (3MH) excretion (a

biological marker of animal protein intake) biological marker of animal protein intake) and BP in 11 Chinese population samples and BP in 11 Chinese population samples

3MH and 3MH/creatinine were inversely 3MH and 3MH/creatinine were inversely associated with BP and hypertension, even associated with BP and hypertension, even after adjustment for age, sex, Na/K ratio, after adjustment for age, sex, Na/K ratio,

BMI, calcium and magnesium.BMI, calcium and magnesium. ““The results provide strong evidence that The results provide strong evidence that

animal protein intake is associated inversely animal protein intake is associated inversely

with BP in Chinese populations.”with BP in Chinese populations.”

Impact of diet on blood pressure and age-related Impact of diet on blood pressure and age-related changes in blood pressure in the US population. changes in blood pressure in the US population.

Hajjar et al.Hajjar et al. Arch Intern Med. 2001;161:589-93Arch Intern Med. 2001;161:589-93.. All individuals >20 yrs old (n = All individuals >20 yrs old (n =

17,030) surveyed in NHANES III 17,030) surveyed in NHANES III Systolic BP and pulse pressure Systolic BP and pulse pressure

positively associated with higher Na, positively associated with higher Na, alcohol, and protein intakes (P<.05) alcohol, and protein intakes (P<.05)

Age-related increase in systolic BP Age-related increase in systolic BP was attenuated by higher Ca and was attenuated by higher Ca and protein intakes.protein intakes.

An increase in dietary protein improves blood An increase in dietary protein improves blood glucose response in persons with type 2 diabetes. glucose response in persons with type 2 diabetes.

Gannon et al. Am J Clin Nutr 78: 734-41Gannon et al. Am J Clin Nutr 78: 734-41..

10 men, 2 women, age 39-72, BMI 22-10 men, 2 women, age 39-72, BMI 22-3737

2250 kcal: 55% CHO, 15 % protein, 2250 kcal: 55% CHO, 15 % protein, 30% fat vs 40% CHO, 30% protein, 30% fat vs 40% CHO, 30% protein, 30% fat30% fat

Glycemic response to high protein diet Glycemic response to high protein diet (AUC) was 40% lower.(AUC) was 40% lower.

Glycated Hb decreased 0.8% at 30% Glycated Hb decreased 0.8% at 30% protein vs 0.3% (p<.05) over 5 weeks. protein vs 0.3% (p<.05) over 5 weeks.

Meat and dairy food consumption and breast Meat and dairy food consumption and breast cancer: a pooled analysis of cohort studies. cancer: a pooled analysis of cohort studies.

Missmera et al.Missmera et al. Int J Epidemiol 2002;31:78-85Int J Epidemiol 2002;31:78-85

Eight prospective cohort studies: 351 041 Eight prospective cohort studies: 351 041 women, 7379 diagnosed with invasive breast women, 7379 diagnosed with invasive breast cancer during 15 years of follow-up.cancer during 15 years of follow-up.

No significant association between intakes No significant association between intakes of total meat, red meat, white meat, total of total meat, red meat, white meat, total dairy fluids, or total dairy solids and breast dairy fluids, or total dairy solids and breast cancer risk. cancer risk.

J-shaped association for egg consumption J-shaped association for egg consumption where, compared to women who did not eat where, compared to women who did not eat eggs, breast cancer risk was slightly eggs, breast cancer risk was slightly decreased among women who consumed <2 decreased among women who consumed <2 eggs per week but slightly increased among eggs per week but slightly increased among women who consumed 1 egg per day.women who consumed 1 egg per day.

Dietary factors and the survival of women with Dietary factors and the survival of women with breast carcinoma.breast carcinoma. Holmes MD, et al. Cancer Holmes MD, et al. Cancer

1999;86:826-351999;86:826-35

1,982 female registered nurses with 1,982 female registered nurses with breast cancer diagnosed between breast cancer diagnosed between 1976-1990 who completed a food 1976-1990 who completed a food frequency questionnaire. frequency questionnaire.

The main outcome measure was time The main outcome measure was time to death from any cause.to death from any cause.

The relative risk (95% confidence The relative risk (95% confidence interval) of mortality comparing interval) of mortality comparing highest with lowest quintile of protein highest with lowest quintile of protein intake was 0.65 (0.47-0.88). intake was 0.65 (0.47-0.88).

Meat, cancer and dietary advice to the Meat, cancer and dietary advice to the public. Hill, Eur J Clin Nutr 2002;56 Suppl public. Hill, Eur J Clin Nutr 2002;56 Suppl

1:S36-411:S36-41 Epidemiological data are consistent with a Epidemiological data are consistent with a

protective role for fruit, vegetables and protective role for fruit, vegetables and whole grain cereals in colon cancer with whole grain cereals in colon cancer with no role for meat consumption as a risk no role for meat consumption as a risk factor.factor.

Meat may play a protective role in gastric Meat may play a protective role in gastric cancer. cancer.

Data from Europe are not consistent with Data from Europe are not consistent with those from the US because of the different those from the US because of the different contexts (meal composition) within which contexts (meal composition) within which meat is consumed in different countriesmeat is consumed in different countries

Meat consumption and colorectal cancer: a review Meat consumption and colorectal cancer: a review of epidemiologic evidence. Noral & Riboli, of epidemiologic evidence. Noral & Riboli,

Nutrition Reviews 2001;59: 37-47Nutrition Reviews 2001;59: 37-47

Review of 36 studies, most show no Review of 36 studies, most show no significant effect for any kind of meat significant effect for any kind of meat

Relative risk ranged from 0.41-2.87Relative risk ranged from 0.41-2.87

Studies with significant adverse association:Studies with significant adverse association: RR 1.33-2.87 for total meat in 5/32 studiesRR 1.33-2.87 for total meat in 5/32 studies RR 1.04-2.35 for red meat in 8/26 studiesRR 1.04-2.35 for red meat in 8/26 studies RR 1.18-2.87 for processed meat in 13/32 RR 1.18-2.87 for processed meat in 13/32

studiesstudies

Protein consumption and bone mineral density in Protein consumption and bone mineral density in

thethe elderly : the Rancho Bernardo Study. elderly : the Rancho Bernardo Study. Promislow et al.Promislow et al. Am J Epidemiol 2002;155:636-44Am J Epidemiol 2002;155:636-44

572 women and 388 men aged 55-92 years. 572 women and 388 men aged 55-92 years. Positive association between animal protein Positive association between animal protein

consumption, assessed by FFQs in 1988-consumption, assessed by FFQs in 1988-1992, and BMD measured 4 years later. 1992, and BMD measured 4 years later.

Negative association between vegetable Negative association between vegetable protein and BMD was observed in both protein and BMD was observed in both sexes. sexes.

Increasing protein consumption appearing Increasing protein consumption appearing to be more beneficial for women with lower to be more beneficial for women with lower calcium intakes, but evidence for this calcium intakes, but evidence for this interaction was not consistently strong. interaction was not consistently strong.

Effect of Protein Intake on Bone Mineralization Effect of Protein Intake on Bone Mineralization during Weight Loss: A 6-Month Trial. Skov et al.during Weight Loss: A 6-Month Trial. Skov et al.

Obesity Research 10:432-8 (2002 Obesity Research 10:432-8 (2002)) 65 overweight adults, 6-month of high 65 overweight adults, 6-month of high

protein (HP: 107.8 g/d)vs low protein (LP: protein (HP: 107.8 g/d)vs low protein (LP: 70.4 g/d) matched fat diets. 70.4 g/d) matched fat diets.

BMC loss, adjusted for differences in fat BMC loss, adjusted for differences in fat loss, was greater in the LP group than in the loss, was greater in the LP group than in the HP group [difference in LP vs. HP, 44.8 g HP group [difference in LP vs. HP, 44.8 g (95% confidence interval, 16 to 73.8 g); p < (95% confidence interval, 16 to 73.8 g); p < 0.05].0.05].

Independent of change in body weight and Independent of change in body weight and composition during the intervention, high composition during the intervention, high protein intake was associated with a protein intake was associated with a diminished loss of BMC (p < 0.01).diminished loss of BMC (p < 0.01).

Protein supplements increase serum IGF-1 levels and Protein supplements increase serum IGF-1 levels and attenuate proximal femur bone loss in patients with recent attenuate proximal femur bone loss in patients with recent

hip fracture. hip fracture. Schurch et al. Ann Int med 1998; 128: 801-9Schurch et al. Ann Int med 1998; 128: 801-9..

82 patients, mean age 80 years, mean 82 patients, mean age 80 years, mean dietary protein 45-51 g/day, recent dietary protein 45-51 g/day, recent femoral fracture, vit D3 200,000 IU femoral fracture, vit D3 200,000 IU givengiven

Supplement: 250 kcal, 20 g protein/35 Supplement: 250 kcal, 20 g protein/35 gm CHO/3 g fat vs 54 g CHO, gm CHO/3 g fat vs 54 g CHO, Ca/Mg/P/A/K1Ca/Mg/P/A/K1

Protein improved femoral healing at 1 Protein improved femoral healing at 1 y, increased IGF-1 and pre-albumeny, increased IGF-1 and pre-albumen

A high dairy protein, high-calcium diet minimizes A high dairy protein, high-calcium diet minimizes bone turnover in overweight adults during weight bone turnover in overweight adults during weight

loss. loss. Bowen et al. J Nutr 2004; 134: 568-573Bowen et al. J Nutr 2004; 134: 568-573

60 subjects (BMI 27-40) lost mean of 60 subjects (BMI 27-40) lost mean of 9.7 kg over 12 weeks on diets of 9.7 kg over 12 weeks on diets of 34% protein, 41% CHO, 24% fat34% protein, 41% CHO, 24% fat

Diet 1: dairy-based, 2400 mg Ca/day. Diet 1: dairy-based, 2400 mg Ca/day. Diet 2, meat-based: 500 mg Ca/dayDiet 2, meat-based: 500 mg Ca/day

Bone resorption markers increased Bone resorption markers increased more with meat-based diet and more with meat-based diet and osteocalcin increased only with osteocalcin increased only with meat-based dietmeat-based diet

Meta-analysis of the effects of Meta-analysis of the effects of soy protein intake on serum lipids.soy protein intake on serum lipids.

Anderson et al NEJM. 1995;333:276-82Anderson et al NEJM. 1995;333:276-82

Meta-analysis of 38 controlled clinical Meta-analysis of 38 controlled clinical trials trials

Soy protein intake averaged 47 g/day. Soy protein intake averaged 47 g/day. Compared with animal protein, soy Compared with animal protein, soy

effect:effect: Total-C decreased 23.2 mg/dl (9.3%, p<.05) Total-C decreased 23.2 mg/dl (9.3%, p<.05) LDL-C decreased 21.7 mg/dl (12.9 %, p<.05)LDL-C decreased 21.7 mg/dl (12.9 %, p<.05) TG decreased 13.3 mg/dl (10.5 %, p<0.05) TG decreased 13.3 mg/dl (10.5 %, p<0.05) HDL-C increased 2.4% (NS). HDL-C increased 2.4% (NS). TC and LDL-C Changes directly related to the TC and LDL-C Changes directly related to the

initial serum cholesterol (P < 0.001)initial serum cholesterol (P < 0.001)

A Dietary Portfolio Approach to Cholesterol A Dietary Portfolio Approach to Cholesterol Reduction. Jenkins et al. Metabolism 2002; 51: Reduction. Jenkins et al. Metabolism 2002; 51:

1596-16041596-1604

7 men, 6 women age 43-84, BMI 21-31, on 7 men, 6 women age 43-84, BMI 21-31, on diets low in saturated fat and cholesteroldiets low in saturated fat and cholesterol

Per 1000 kcal:Per 1000 kcal: Soy protein 22.7 gSoy protein 22.7 g Viscous fiber 8.2 g (oats, barley, psyllium, Viscous fiber 8.2 g (oats, barley, psyllium,

okra, eggplant)okra, eggplant) Plant sterols 1 g (margarine)Plant sterols 1 g (margarine) Raw unblanched almonds 2.9 gRaw unblanched almonds 2.9 g

LDL-C decreased 29% (p<.001), LDL/HDL LDL-C decreased 29% (p<.001), LDL/HDL decreased 26.5% (p<.001)decreased 26.5% (p<.001)

Legume consumption and risk of coronary heart Legume consumption and risk of coronary heart disease in US men and women. Bazzano et al. disease in US men and women. Bazzano et al.

Arch Intern Med. 2001;161:2573-8Arch Intern Med. 2001;161:2573-8 9632 men and women who participated in NHANES 1 9632 men and women who participated in NHANES 1

and were free of CVDand were free of CVD Frequency of legume intake was estimated using a 3-Frequency of legume intake was estimated using a 3-

month food frequency questionnaire, month food frequency questionnaire, 19 years of follow-up, 1802 incident cases of CHD 19 years of follow-up, 1802 incident cases of CHD

and 3680 incident cases of CVD were documented. and 3680 incident cases of CVD were documented. Legume consumption was significantly and inversely Legume consumption was significantly and inversely

associated with risk of CHD (P =.002 for trend) and associated with risk of CHD (P =.002 for trend) and CVD (P =.02 for trend) after adjustment for CVD (P =.02 for trend) after adjustment for established CVD risk factors. established CVD risk factors.

Legume consumption 4 times or more per week Legume consumption 4 times or more per week compared with less than once a week was associated compared with less than once a week was associated with a 22% lower risk of CHD (relative risk, 0.78; 95% with a 22% lower risk of CHD (relative risk, 0.78; 95% confidence interval, 0.68-0.90) and an 11% lower risk confidence interval, 0.68-0.90) and an 11% lower risk of CVD (relative risk, 0.89; 95% confidence interval, of CVD (relative risk, 0.89; 95% confidence interval, 0.80-0.98). 0.80-0.98).

The Impact of protein on renal function decline in women The Impact of protein on renal function decline in women with normal renal function or mild renal insufficiency.with normal renal function or mild renal insufficiency.

Knight et al, Ann Int med 2003; 138: 460-7Knight et al, Ann Int med 2003; 138: 460-7

1624 nurses age 42-68, followed for 11 1624 nurses age 42-68, followed for 11 years, protein intake measured by FFQ years, protein intake measured by FFQ (mean 76 g/d)(mean 76 g/d)

GFR estimated from serum creatinine, GFR estimated from serum creatinine, age, height, weight by 2 formulasage, height, weight by 2 formulas

No effect of protein on GFR in women with No effect of protein on GFR in women with baseline GFR>80 ml/min/1.73 m-squared.baseline GFR>80 ml/min/1.73 m-squared.

Initial GFR of 55-80 ml/min (S-Initial GFR of 55-80 ml/min (S-creatinine .77-1.1mg/dl, mean .88) showed creatinine .77-1.1mg/dl, mean .88) showed a decline in GFR of 7.72 ml/min/10 g a decline in GFR of 7.72 ml/min/10 g increase in protein. Meat protein>dairy increase in protein. Meat protein>dairy protein. No effect of vegetable protein. protein. No effect of vegetable protein.

Purine-Rich foods, Dairy and Protein Intake, Purine-Rich foods, Dairy and Protein Intake, and the Risk of Gout in Men. Choi et al, NEJM and the Risk of Gout in Men. Choi et al, NEJM

2004; 350: 1093-11032004; 350: 1093-1103

47,150 men followed for 12 years47,150 men followed for 12 years Incidence of gout increased with increasing Incidence of gout increased with increasing

intake of protein from meat or seafood and intake of protein from meat or seafood and decreased with increasing intake of dairy decreased with increasing intake of dairy protein. No effect of total proteinprotein. No effect of total protein

Relative risk:Relative risk:

1.41 for 2.5 vs 0.5 meat servings/day1.41 for 2.5 vs 0.5 meat servings/day

1.51 for 0.8 vs 0.04 seafood servings/day1.51 for 0.8 vs 0.04 seafood servings/day

0.56 for 4.2 vs 0.5 dairy servings/day0.56 for 4.2 vs 0.5 dairy servings/day

Protein Consumption May Protein Consumption May Affect Mineral BioavailabilityAffect Mineral Bioavailability

High meat diets increase zinc High meat diets increase zinc bioavailability in elderly women bioavailability in elderly women (Hunt et (Hunt et

al, Am J Clin Nutr 1995; 62: 621-32)al, Am J Clin Nutr 1995; 62: 621-32) and iron and iron and zinc utilization in young women, and zinc utilization in young women, with no effect above 3 oz lean beef/d. with no effect above 3 oz lean beef/d. (Johnson & Walker, J Am Diet Assoc 1992; 92: 1474-(Johnson & Walker, J Am Diet Assoc 1992; 92: 1474-8).8).

Replacement of 25% meat protein by Replacement of 25% meat protein by soy protein decreased zinc absorption soy protein decreased zinc absorption and protein digestibility and protein digestibility (Sandstrom et al, J (Sandstrom et al, J Nutr 1986; 116: 2209-18)Nutr 1986; 116: 2209-18)

Large Neutral Amino Acids Large Neutral Amino Acids Share Common Share Common TransportersTransporters The ratio of tryptophan to leucine, The ratio of tryptophan to leucine,

isoleucine, valine, phenylalanine isoleucine, valine, phenylalanine and tyrosine (5LNAA) influences and tyrosine (5LNAA) influences brain serotonin concentrationbrain serotonin concentration

Exercise and CHO loading raise Exercise and CHO loading raise this ratiothis ratio

High protein diets lower this ratioHigh protein diets lower this ratio Control of brain serotonin by the diet. Control of brain serotonin by the diet.

Wurtman RJ, Fernstrom JD. Adv Neurol Wurtman RJ, Fernstrom JD. Adv Neurol 1974;5:19-291974;5:19-29

Implications of Competitive Implications of Competitive Transport of LNAA into Transport of LNAA into

BrainBrain Tryptophan/5LNAA is lower in major Tryptophan/5LNAA is lower in major

depression, correlates with severity of depression, correlates with severity of depression and with plasma cortisol depression and with plasma cortisol level following dexamethasone level following dexamethasone suppression.suppression.

Tryptophan/5LNAA is higher after Tryptophan/5LNAA is higher after strenuous exercise and in patients strenuous exercise and in patients with fibromyalgia, correlates with with fibromyalgia, correlates with intensity of post-exertional fatigue, intensity of post-exertional fatigue, reversible with BCAA feedingreversible with BCAA feeding

References on LNAA References on LNAA TransportTransport

Decreased plasma tryptophan concentration in major Decreased plasma tryptophan concentration in major depression: relationship to melancholia and weight loss. depression: relationship to melancholia and weight loss. Anderson IM, et al.Anderson IM, et al. J Affect Disord 1990;20:185-91 J Affect Disord 1990;20:185-91

Relationship between the dexamethasone suppression test Relationship between the dexamethasone suppression test and the L-tryptophan/competing amino acids ratio in and the L-tryptophan/competing amino acids ratio in depression. Maes M, et al.depression. Maes M, et al. Psychiatry Res 1987;21:323-35 Psychiatry Res 1987;21:323-35

Plasma tryptophan and five other amino acids in depressed Plasma tryptophan and five other amino acids in depressed and normal subjects.and normal subjects. DeMyer MK, et al DeMyer MK, et al Arch Gen Psychiatry Arch Gen Psychiatry 1981;38:642-61981;38:642-6

Serotonergic markers and lowered plasma branched-chain-Serotonergic markers and lowered plasma branched-chain-amino acid concentrations in fibromyalgia. Maes M, et alamino acid concentrations in fibromyalgia. Maes M, et al Psychiatry Res 2000; 4;97:11-20Psychiatry Res 2000; 4;97:11-20..

Amino acids and central fatigue. Blomstrand E.Amino acids and central fatigue. Blomstrand E. Amino Acids Amino Acids 2001;20(1):25-34 2001;20(1):25-34

Glutathione (GSH) Levels Depend Glutathione (GSH) Levels Depend Upon Dietary Sulfur Amino AcidsUpon Dietary Sulfur Amino Acids

GSH/GSSG is the major human GSH/GSSG is the major human redox pairredox pair

Malnutrition, fasting and Malnutrition, fasting and alcoholism deplete hepatic and alcoholism deplete hepatic and WBC GSH levelsWBC GSH levels

Depletion of GSH impairs immune Depletion of GSH impairs immune function and detoxification of function and detoxification of substrates like acetaminophensubstrates like acetaminophen

Loading with sulfur AA reverses Loading with sulfur AA reverses these effectsthese effects

ConclusionsConclusions High protein intake (up 30% of kcal) High protein intake (up 30% of kcal)

is not detrimental and may produce is not detrimental and may produce improved health outcomes.improved health outcomes.

Dairy and vegetable protein may have Dairy and vegetable protein may have different effects than meat protein.different effects than meat protein.

Elderly patients often consume too Elderly patients often consume too little protein and should be little protein and should be encouraged to increase intake to >1 encouraged to increase intake to >1 gm/kg/day (pulse feeding of 0.8 g/kg gm/kg/day (pulse feeding of 0.8 g/kg at one meal may work best: Arnal et at one meal may work best: Arnal et al, Am J Clin Nutr 1999; 69: 1202-8)al, Am J Clin Nutr 1999; 69: 1202-8)