Transcript Protein Nutrition - What is Integrated Medicine?

Protein and Amino Acids
Leo Galland, M.D., F.A.C.P., F.A.C.N.
Foundation for Integrated Medicine
How much protein does a person really need?
Does the source of protein matter?
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“Few issues in nutritional science have aroused
such long-standing and deep-seated
controversies as protein and amino acid
requirements.”
Millward, J Nutr 1997
The Elements of Life
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Carbon
Oxygen
Hydrogen
Nitrogen
Sulfur
Phosphorus
“Minerals”: Ca, Mg, Na, K, Fe, Zn, Cu, Se, Mn, Cr, Mo,
Vn, Ni...
Essential Amino Acids
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Isoleucine
Leucine
Lysine
Methionine*
Phenylalanine*
Threonine
Tryptophan
Valine
Arginine*
Histidine
Major Non-essential Amino Acids
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Alanine
Asparagine
Aspartate
Cysteine
Glutamate
Glutamine
Glycine
Proline
Serine
Tyrosine
The Fate of Dietary Protein
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Digestion and absorption (efficiency varies by
25%, depending upon protein source)
Maintenance of body protein stores
Net protein synthesis (less than 10% of
minimum requirements, even in children)
Synthesis of non-protein compounds
Oxidative deamination
Essential Non-Protein
Nitrogen-Requiring Processes
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Nucleic acid synthesis, including adenosine for ATP
(glutamate, aspartate, glycine, glutamine)
Nervous system: Neurotransmitter/neuropeptide
synthesis (phenylalanine, tryptophan, glutamate….)
Immune system: Cytokine production,Anti-oxidant
protection (taurine; glutathione: cysteine, glutamate,
glycine)
Skeletal muscle: Creatine (methionine, arginine, glycine)
Cardiovascular system: Nitric oxide synthesis (arginine)
GI tract: Mucin secretion (threonine, cysteine, serine,
proline)
How dietary protein is recorded:
 grams/day
 mg/kg
%
[50-135]
body weight [800-1500]
of kcalories consumed [10-20]
Minimum Protein Requirements
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Obligatory Nitrogen Loss (metabolic ward)
36 mg/kg/day urinary (85%)
12 mg/kg.day fecal (13%)
8 mg/kg/day sweat, skin, saliva, hair (2%)
54 mg of nitrogen/kg/day total
Replacement requires 340 mg protein/kg/day
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70 kg person: 24 gm/day
WHO safe minimum: 750 mg/kg/day, of which 84
mg/kg should be essential amino acids
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70 kg person = 52 gm/day
60 kg person = 46 gm/day
Minimum Safe Protein
Requirements for Children
Newborns 1.85 mg/kg/day
 Infants: 1.5-1.65 gm/kg/day
 Toddlers: 1.1-1.2 mg/kg/day
 School children: 1.0 mg/kg/day
 Adolescents 0.9-0.95 mg/kg/day
N-balance depends upon caloric intake. Fewer
calories increase protein needs. Profound interindividual differences
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US Adult Protein RDA's
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female
Calories 1900-2200 2300-2900
46 gm
71 gm
about 10% of calories
typical US diet: 15% of calories
popular weight loss diets: 30% of calories
excess protein is oxidized by deamination
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Protein
male
Ketogenic Amino Acids
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Exclusively ketogenic:
Leucine
Lysine
Ketogenic and glucogenic:
Threonine
Isoleucine
Phenylalanine
Tyrosine
Tryptophan
Hunter-Gatherer Diets
Compared to typical U.S. diet:
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high dietary protein (19-35% of calories)
relatively low level of dietary carbohydrate (2240% of calories)
variable fat intake (28-58% of calories)
The paradoxical nature of hunter-gatherer diets: meat-based, yet
non-atherogenic L Cordain, S B Eaton, et al Eur J Clin Nutr 2002; 56,
Suppl 1, S42-S52
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13 known quantitative dietary studies of HG
demonstrate that animal food provided the
dominant (65%) energy source, while gathered
plant foods comprised the remainder (35%).
Comprehensive review of 229 HG societies:
mean subsistence dependence upon gathered
plant foods was 32%, whereas it was 68% for
animal foods.
Changes in nutritional status and patterns of morbidity among freeliving elderly persons: a 10-year study. Vellas et al, Nutr 1997;
13 :515-9
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304 healthy French elderly (median age 72 in
1980): 97 (34.2%) remained healthy;74 (26.5%)
became frail or sick; 54 (19.1%) died, 57 (20.1%)
dropped out. Median protein intake was 0.8-1.2
g/kg of body weight in 1980-81.
Protein intake 1.20-1.76 g/kg associated with
fewer health problems over the next 10 years vs
protein intakes < 0.8 g/kg
High-protein low fat diets are effective for weight loss and favorably
affect biomarkers in healthy adults. Johnson et al. J Nutr 2003; 134:
586-91. 2003;
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20 adults, low fat (<30% kcal) diets, consuming
either 10% or 30% protein
Weight loss (-6% over 6 weeks) and fat loss (-9
to -11%) not affected by protein
Cholesterol (-10 to -12%), insulin (-25%), uric
acid (-22 to -30%) similar changes
Hunger and satiety better with high protein
Ca-balance unaffected, N-balance better
A Reduced Ratio of Dietary Carbohydrate to Protein Improves Body
Composition and Blood Lipid Profiles during Weight Loss in Adult Women.
Layman DK. J.Nutr. 2003; 133:411-417
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24 women age 45 to 56, BMI >26 kg/m2
Isocaloric, matched-fat diets, 68 vs 125 g protein/day for 10 weeks.
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 (21%)
LP had higher insulin responses to meals and postprandial
hypoglycemia
HP reported greater satiety.
Increasing the proportion of protein to CHO in the diet of adult
women has positive effects on body composition, blood lipids, glucose
homeostasis and satiety during weight loss.
Randomized trial on protein vs carbohydrate in ad libitum fat
reduced diet for the treatment of obesity. Skov et al. Int J Obes
1999; 50:418-30
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50 subjects, protein of 12% vs 25% of kcal,
mean BMI of 30.8 and 30.0.
27 week weight loss: high protein 8.9 kg, high
CHO 5.1 kg
27 week fat loss: high protein 7.6 kg, high CHO
4.3 kg (84-85% of total weight loss)
Kcal consumed: 2139 high protein vs 2605 high
CHO.
Dietary protein and risk of ischemic heart disease in women. Hu et
al, Amer J Clin Nutr, 1999. 70: 221-7
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80,082 women aged 34–59 y
Median protein 14.7% of kcal to 24.0% of kcal by quintile. Higher
protein associated with less tobacco and alcohol use, more exercise and
multivitamin and vit E supplements, more fat, saturated fat,
cholesterol, folate, meat, dark bread, fruits and vegetables, and less
carbohydrate (white bread, potatoes, sweets and desserts.)
High protein intakes reduced risk of ischemic heart disease: RR 0.74
(95%). Both animal and vegetable protein contributed to the lower risk,
but most of the protein came from animal sources. This inverse
association was similar in women with low- or high-fat diets.
Conclusion: Increased dietary protein does not increase and may
reduce risk of ischemic heart disease.
Short-term effects of substituting protein for carbohydrate in the diets of
moderately hypercholesterolemic human subjects. Wolfe BM, Giovannetti PM.
Metabolism 1991 Apr;40(4):338-43.
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Hypercholesterolemic human subjects (four men,
six women)
Diets: 23% v 11% of energy as protein, 24% as fat,
53% v 65% as carbohydrate. Isocaloric substitution
of protein for CHO during low fat diet
High protein: HDL-C higher by 12% (p<.01),
total cholesterol (TC) lower by 6.5% (p< .001),
LDL-C lower by 6.4% (p<.02), TG lower by 23%
(p<.02). LDL-C/HDL-C lower by 17% (p<.001).
Cardiovascular Disease and Diabetes: Inverse relationship between urinary markers of
animal protein intake and
blood pressure in Chinese: results from the WHO Cardiovascular Diseases and Alimentary
Comparison (CARDIAC) Study.
Liua L et al, Int J Epidemiology 2002;31:227-233
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Urinary 3-methylhistidine (3MH) excretion (a biological
marker of animal protein intake) and BP in 11 Chinese
population samples
3MH and 3MH/creatinine were inversely associated with
BP and hypertension, even after adjustment for age, sex,
Na/K ratio, BMI, calcium and magnesium.
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“The results provide strong evidence that animal protein
intake is associated inversely with BP in Chinese
populations.”
Impact of diet on blood pressure and age-related changes in blood
pressure in the US population.
Hajjar et al. Arch Intern Med. 2001;161:589-93.
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All individuals >20 yrs old (n = 17,030)
surveyed in NHANES III
Systolic BP and pulse pressure positively
associated with higher Na, alcohol, and protein
intakes (P<.05)
Age-related increase in systolic BP was
attenuated by higher Ca and protein intakes.
An increase in dietary protein improves blood glucose response in
persons with type 2 diabetes.
Gannon et al. Am J Clin Nutr 78: 734-41.
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10 men, 2 women, age 39-72, BMI 22-37
2250 kcal: 55% CHO, 15 % protein, 30% fat vs
40% CHO, 30% protein, 30% fat
Glycemic response to high protein diet (AUC)
was 40% lower.
Glycated Hb decreased 0.8% at 30% protein vs
0.3% (p<.05) over 5 weeks.
Meat and dairy food consumption and breast cancer: a pooled
analysis of cohort studies. Missmera et al.
Int J Epidemiol 2002;31:78-85
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Eight prospective cohort studies: 351 041 women, 7379
diagnosed with invasive breast cancer during 15 years of
follow-up.
No significant association between intakes of total meat,
red meat, white meat, total dairy fluids, or total dairy solids
and breast cancer risk.
J-shaped association for egg consumption where,
compared to women who did not eat eggs, breast cancer
risk was slightly decreased among women who consumed
<2 eggs per week but slightly increased among women who
consumed 1 egg per day.
Dietary factors and the survival of women with breast carcinoma.
Holmes MD, et al. Cancer 1999;86:826-35
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1,982 female registered nurses with breast cancer
diagnosed between 1976-1990 who completed a
food frequency questionnaire.
The main outcome measure was time to death
from any cause.
The relative risk (95% confidence interval) of
mortality comparing highest with lowest quintile
of protein intake was 0.65 (0.47-0.88).
Meat, cancer and dietary advice to the public. Hill, Eur J
Clin Nutr 2002;56 Suppl 1:S36-41
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Epidemiological data are consistent with a
protective role for fruit, vegetables and whole grain
cereals in colon cancer with no role for meat
consumption as a risk factor.
Meat may play a protective role in gastric cancer.
Data from Europe are not consistent with those
from the US because of the different contexts
(meal composition) within which meat is
consumed in different countries
Meat consumption and colorectal cancer: a review of
epidemiologic evidence. Noral & Riboli,
Nutrition Reviews 2001;59: 37-47
Review of 36 studies, most show no significant
effect for any kind of meat
 Relative risk ranged from 0.41-2.87
Studies with significant adverse association:
 RR 1.33-2.87 for total meat in 5/32 studies
 RR 1.04-2.35 for red meat in 8/26 studies
 RR 1.18-2.87 for processed meat in 13/32
studies
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Protein consumption and bone mineral density in the elderly : the
Rancho Bernardo Study. Promislow et al. Am J Epidemiol
2002;155:636-44
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572 women and 388 men aged 55-92 years.
Positive association between animal protein consumption,
assessed by FFQs in 1988-1992, and BMD measured 4 years
later.
Negative association between vegetable protein and BMD
was observed in both sexes.
Increasing protein consumption appearing to be more
beneficial for women with lower calcium intakes, but
evidence for this interaction was not consistently strong.
Effect of Protein Intake on Bone Mineralization during Weight
Loss: A 6-Month Trial. Skov et al.
Obesity Research 10:432-8 (2002)
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65 overweight adults, 6-month of high protein (HP: 107.8
g/d)vs low protein (LP: 70.4 g/d) matched fat diets.
BMC loss, adjusted for differences in fat loss, was greater
in the LP group than in the HP group [difference in LP vs.
HP, 44.8 g (95% confidence interval, 16 to 73.8 g); p < 0.05].
Independent of change in body weight and composition
during the intervention, high protein intake was associated
with a diminished loss of BMC (p < 0.01).
Protein supplements increase serum IGF-1 levels and attenuate proximal femur
bone loss in patients with recent hip fracture.
Schurch et al. Ann Int med 1998; 128: 801-9.
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82 patients, mean age 80 years, mean dietary
protein 45-51 g/day, recent femoral fracture, vit
D3 200,000 IU given
Supplement: 250 kcal, 20 g protein/35 gm
CHO/3 g fat vs 54 g CHO, Ca/Mg/P/A/K1
Protein improved femoral healing at 1 y,
increased IGF-1 and pre-albumen
A high dairy protein, high-calcium diet minimizes bone turnover in
overweight adults during weight loss.
Bowen et al. J Nutr 2004; 134: 568-573
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60 subjects (BMI 27-40) lost mean of 9.7 kg
over 12 weeks on diets of 34% protein, 41%
CHO, 24% fat
Diet 1: dairy-based, 2400 mg Ca/day. Diet 2,
meat-based: 500 mg Ca/day
Bone resorption markers increased more with
meat-based diet and osteocalcin increased only
with meat-based diet
Meta-analysis of the effects of
soy protein intake on serum lipids.
Anderson et al NEJM. 1995;333:276-82
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Meta-analysis of 38 controlled clinical trials
Soy protein intake averaged 47 g/day.
Compared with animal protein, soy effect:
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Total-C decreased 23.2 mg/dl (9.3%, p<.05)
LDL-C decreased 21.7 mg/dl (12.9 %, p<.05)
TG decreased 13.3 mg/dl (10.5 %, p<0.05)
HDL-C increased 2.4% (NS).
TC and LDL-C Changes directly related to the initial
serum cholesterol (P < 0.001)
A Dietary Portfolio Approach to Cholesterol Reduction. Jenkins et
al. Metabolism 2002; 51: 1596-1604
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7 men, 6 women age 43-84, BMI 21-31, on diets low in
saturated fat and cholesterol
Per 1000 kcal:
 Soy protein 22.7 g
 Viscous fiber 8.2 g (oats, barley, psyllium, okra,
eggplant)
 Plant sterols 1 g (margarine)
 Raw unblanched almonds 2.9 g
LDL-C decreased 29% (p<.001), LDL/HDL decreased
26.5% (p<.001)
Legume consumption and risk of coronary heart disease in US men
and women. Bazzano et al.
Arch Intern Med. 2001;161:2573-8
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9632 men and women who participated in NHANES 1 and were free of
CVD
Frequency of legume intake was estimated using a 3-month food
frequency questionnaire,
19 years of follow-up, 1802 incident cases of CHD and 3680 incident
cases of CVD were documented.
Legume consumption was significantly and inversely associated with
risk of CHD (P =.002 for trend) and CVD (P =.02 for trend) after
adjustment for established CVD risk factors.
Legume consumption 4 times or more per week compared with less
than once a week was associated with a 22% lower risk of CHD
(relative risk, 0.78; 95% confidence interval, 0.68-0.90) and an 11% lower
risk of CVD (relative risk, 0.89; 95% confidence interval, 0.80-0.98).
The Impact of protein on renal function decline in women with normal renal
function or mild renal insufficiency.
Knight et al, Ann Int med 2003; 138: 460-7
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1624 nurses age 42-68, followed for 11 years, protein
intake measured by FFQ (mean 76 g/d)
GFR estimated from serum creatinine, age, height,
weight by 2 formulas
No effect of protein on GFR in women with baseline
GFR>80 ml/min/1.73 m-squared.
Initial GFR of 55-80 ml/min (S-creatinine .771.1mg/dl, mean .88) showed a decline in GFR of 7.72
ml/min/10 g increase in protein. Meat protein>dairy
protein. No effect of vegetable protein.
Purine-Rich foods, Dairy and Protein Intake, and the Risk of
Gout in Men. Choi et al, NEJM 2004; 350: 1093-1103
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47,150 men followed for 12 years
Incidence of gout increased with increasing intake of
protein from meat or seafood and decreased with
increasing intake of dairy protein. No effect of total
protein
Relative risk:
1.41 for 2.5 vs 0.5 meat servings/day
1.51 for 0.8 vs 0.04 seafood servings/day
0.56 for 4.2 vs 0.5 dairy servings/day
Protein Consumption May Affect
Mineral Bioavailability
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High meat diets increase zinc bioavailability in
elderly women (Hunt et al, Am J Clin Nutr 1995; 62: 621-32) and
iron and zinc utilization in young women, with no
effect above 3 oz lean beef/d. (Johnson & Walker, J Am
Diet Assoc 1992; 92: 1474-8).
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Replacement of 25% meat protein by soy protein
decreased zinc absorption and protein digestibility
(Sandstrom et al, J Nutr 1986; 116: 2209-18)
Large Neutral Amino Acids Share
Common Transporters
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The ratio of tryptophan to leucine,
isoleucine, valine, phenylalanine and
tyrosine (5LNAA) influences brain serotonin
concentration
Exercise and CHO loading raise this ratio
High protein diets lower this ratio
Control of brain serotonin by the diet. Wurtman RJ,
Fernstrom JD. Adv Neurol 1974;5:19-29
Implications of Competitive
Transport of LNAA into Brain
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Tryptophan/5LNAA is lower in major depression,
correlates with severity of depression and with
plasma cortisol level following dexamethasone
suppression.
Tryptophan/5LNAA is higher after strenuous
exercise and in patients with fibromyalgia,
correlates with intensity of post-exertional fatigue,
reversible with BCAA feeding
References on LNAA Transport
Decreased plasma tryptophan concentration in major depression: relationship to
melancholia and weight loss. Anderson IM, et al. J Affect Disord 1990;20:185-91
Relationship between the dexamethasone suppression test and the Ltryptophan/competing amino acids ratio in depression. Maes M, et al.
Psychiatry Res 1987;21:323-35
Plasma tryptophan and five other amino acids in depressed and normal subjects.
DeMyer MK, et al Arch Gen Psychiatry 1981;38:642-6
Serotonergic markers and lowered plasma branched-chain-amino acid
concentrations in fibromyalgia. Maes M, et al Psychiatry Res 2000; 4;97:11-20.
Amino acids and central fatigue. Blomstrand E. Amino Acids 2001;20(1):25-34
Glutathione (GSH) Levels Depend Upon
Dietary Sulfur Amino Acids
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GSH/GSSG is the major human redox pair
Malnutrition, fasting and alcoholism deplete
hepatic and WBC GSH levels
Depletion of GSH impairs immune function
and detoxification of substrates like
acetaminophen
Loading with sulfur AA reverses these
effects
Conclusions
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High protein intake (up 30% of kcal) is not
detrimental and may produce improved health
outcomes.
Dairy and vegetable protein may have different
effects than meat protein.
Elderly patients often consume too little protein
and should be encouraged to increase intake to >1
gm/kg/day (pulse feeding of 0.8 g/kg at one meal
may work best: Arnal et al, Am J Clin Nutr 1999;
69: 1202-8)