[PDF] - Nutrition and Bone: Protein, Sodium Chloride, and Other Nutrients PDF Document

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Nutrition and Bone: Protein, Sodium Chloride, and Other Nutrients

Deborah E. Sellmeyer, MD Associate Professor of Medicine Johns Hopkins School of Medicine

Acid Base Balance and Skeletal Health

Acid precursors: sulfur containing amino acids in all proteins
Base precursors: alkaline potassium salts in fruit/vegetables

(Kcitrate, KHCO3)

Does exposure to a net dietary acid load mobilize base from

bone to titrate dietary acid?

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Long-term Potential Effects

f a Net Dietary Acid Load
Skeleton

– Physiochemical effect – Cell mediated

Muscle

–  IGF-1 – Mobilization of glutamine

Effects of age-related decline in renal function
? Net effect = bone / muscle loss

Relationship is Complex

Primary focus on protein (acid)
Protein only half the equation: hunter-gatherer diets

– ~250 g/d protein – typically net base producing

Hunter-gatherer diet = 88 meq/day base
Western diet = 58 meq/day acid

Sebastian A et. al. Am J Clin Nutr. 2002 Dec;76(6):1308-16.

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Sulfur-containing AA (g) per 10g Protein

0.00 0.10 0.20 0.30 0.40 almonds peas peanut butter Grt North beans soybeans milk cottage cheese ground beef english muffin chicken white rice haddock spaghetti noodles

Improving Dietary Acid-Base Balance

Option 1: Less acid

–Reduce dietary protein, cereal grains –Protein important for peak bone mass, skeletal maintenance, healing

Option 2: More base

–Dietary (potassium-rich fruit / veggies) –Alkaline potassium supplements

Potassium bicarbonate
Potassium citrate

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Alkaline K Salts and Ca Metabolism

 Urine calcium excretion
Calcium balance = dietary calcium intake –

(urine calcium + fecal calcium) – n=10, KHCO3

60 mmol/d x 12 days
Ca balance = + 36 mg/day

– n=18, KHCO3

60-120 mmol/day x 18 days
Ca balance = + 56 mg/day

– Intestinal absorption not directly measured

Lemann J Jr, et al. Kidney Int 1989 Feb;35(2):688-95. Sebastian A et. al. N Engl J Med 1994;330:1776-1781

Alkaline K Salts and Ca Metabolism

Intestinal fractional calcium absorption

(oral / IV stable isotopes) – n=18, KCitrate 40 mmol/d x 14 days

No effect on fractional calcium absorption

– x-sectional, n=191, free living diet

Potassium intake inversely

associated with calcium absorption

Potassium from milk / meat

rather than fruit / veggies

Sakhaee K, et. al. J Clin Endocrinol Metab. 2005 Jun;90(6):3528-33 Rafferty K, et al. J Am Coll Nutr. 2005 Apr;24(2):99-106

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Calcium Absorption and Balance 6 Month Intervention

*p<0.05 compared to placebo 40 20

20
40
60
80
100

Change in urine calcium excretion (mg/day) Change in fractional calcium absorption (%) Change in calcium balance (mg/day) 10 8 6 4 2

2
4
6

250 200 150 100 50

50
100
150

* * *

Placebo KCitrate 60 mmol/day KCitrate 90 mmol/day

Moseley KF, et al. J Bone Miner Res. 2013 Mar;28(3):497-504.

Markers of Bone Turnover

Placebo K Citrate 60 mmol/day K Citrate 90 mmol/day BsAP (μg/L) Baseline Change 11.8 + 1.3

0.95 + 0.8

11.8 + 1.3

1.1 + 0.9

11.3 + 1.1

1.8 + 0.8

Serum CTX (ng/ml) Baseline Change 0.19 + 0.04 0.04 + 0.03 0.25 + 0.03

0.07 + 0.04a

0.25 + 0.04

0.03 + 0.04a

ap<0.05 vs. placebo Moseley KF, et al. J Bone Miner Res. 2013 Mar;28(3):497-504.

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KCitrate and BMD

Jehle S, et. al. J Am Soc Nephrol. 2006 Nov;17(11):3213-22

161 postmenopausal women 30 mmol/day Lumbar Spine Total Hip

+ 1% 0%

1%
2%

3 Months 6 Months 9 Months 12 Months

+ 1% 0%

1%

1.9% p<0.001 2.0% p<0.001 KCl KCitrate

KCitrate and BMD

Macdonald HM, et al. Am J Clin Nutr. 2008 Aug;88(2):465-74

276 postmenopausal women KCitrate 55.5 mmol/d, 18.5 mmol/d, fruit / veggies, placebo No effect BMD, urine calcium

Placebo Fruit / Veggies KCitrate 55.5 mmol KCitrate 18.5 mmol

0.0

0.5
1.0
1.5
2.0
2.5
3.0

Lumbar Spine Total Hip

2-year BMD change (%)

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Jehle S, et. al. J Clin Endocrinol Metab. 2013 Jan;98(1):207-17.

N=201 60% female 25(OH)vit D = 24 + 8 ng/ml L Spine T-score = -0.6 + 1.5 Kcitrate 60 mmol/day vs. pbo NAE negative on Kcitrate ↑ trabecular thickness, number on QCT.

L2-L4

n=91 n=84 n=86 n=87 n=91 n=85 n=86 n=87 1.7% (1.0-2.3)

24 18 12 6

2
1.5
1
0.5

0.5 1 1.0 2 2.5 3 Kcitrate Placebo Months % Change in BMD †† †† † xx xx xx 24 18 12 6

n=91 n=84 n=86 n=87 n=90 n=85 n=86 n=87 1.0% (0.5-1.5)

2

1 0.5

0.5
1
1.5

2 1.5 Kcitrate Placebo

Total Hip

% Change in BMD Months † x † x † xx x=p<0.05; xx=p<0.001, Kcitrate vs. placebo †=p<0.05;††=p<0.001, compared to baseline

KCitrate and BMD

Isoflavones/Soy

Plant compounds (phytoestrogens) found in

soybeans, clover, alfalfa sprouts

Studies on bone health mixed

– Interventions varied – Different compounds may offset each other – Effects may depend on proximity to menopause – Equol producers – 2 placebo controlled RCTs neg

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Sodium Chloride

 dietary NaCl  urine calcium, bone resorption
Effects on fracture not known
Dietary K and base (fruit and vegetables) offset

NaCl effects

High salt foods:

– prepared foods--jars, cans, boxes, bottles – condiments, sauces – cheese, bread – restaurants

Current RDA: 1500mg/day; AHA rec: 2400mg/day

Phosphorus

Essential for bone building and growth
85% of body’s P bound to skeleton
Excess PO4   PTH  ? bone resorption
Typical intakes > RDA (700 mg/day)
PO4 intake ’ing due to preservatives
High dietary Ca  absorption dietary PO4
Meat, poultry, fish, eggs, dairy, nuts, legumes,

cereals, grains, cola

Typical intakes (1000-1500 mg/day) prob OK unless

dietary Ca low

Poor overall nutrition = low PO4 intake
? important during anabolic osteoporosis tx

Relationship to Skeleton The Issues Sources Bottom Line

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Magnesium

Essential for bone formation
2/3 of body’s Mg in skeleton (surface)
Impt for proper crystal formation during mineralization
Deficiency  impairs PTH secretion  hypocalcemia,

vitamin D resistance

Typical intakes < RDA
RDA 320 mg women, 420 mg men, +35 mg preg
Whole grains, green vegetables, squash, nuts, seeds,

“hard” water

Typical intakes appear low
EtOH  Mg wasting
Effect on skeletal health not clear

Sources Bottom Line The Issues Relationship to Skeleton

Iron

Co-factor for enzymes involved in collagen synthesis
 bone strength Fe deficient rats
Fe absorption decreased by other minerals esp Ca
Fe overload states associated with  trabecular

volume, number, thickness

Dark green veg, spinach, red meat
Separate Fe and calcium supplements
Unclear how much of bone deficits in overload states

due to Fe itself

Sources Bottom Line Relationship to Skeleton The Issues

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Zinc

Co-factor for enzymes involved in collagen synthesis

and mineralization

 bone formation Zn deficient rats
Low Zn levels associated with osteoporosis in humans
Zn supplements improved BMD in rats
Red meat, poultry, fish, oysters, eggs, legumes, whole

grain breads, milk

Zn stims osteoblasts, bone formation in animal studies
EtOH  Zn wasting
Need human intervention studies

Sources Bottom Line Relationship to Skeleton The Issues

Copper

Involved in collagen maturation, cross linking
Typical intakes < RDA
Cu deficiency assoc with  osteoblast function
Trace mineral supplement incl Cu increased BMD
Legumes, nuts, mushrooms, liver, oysters, cereals,

chocolate

Need human intervention studies

Sources Bottom Line Relationship to Skeleton The Issues

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Vitamin A and Carotenoids

Vitamin A involved in bone remodeling process
Animal foods: retinol; vegetables: carotenoids
Excess and deficiency Vit A  skeletal fragility
 intakes/ serum retinol levels associated with  BMD,

 fracture in some human studies

β-carotene, lycopene, leutein assoc with  BMD,

 bone loss,  hip fracture

red/orange/yellow vegetables (β-carotene), dark green

veg (lutein), tomatoes, watermelon (lycopene), liver, dairy products, fish

Avoid excess or insufficient Vit A intake (3000 IU per

day in supplements)

Vegetable sources also provide antioxidants

Sources Bottom Line Relationship to Skeleton The Issues

Vitamin B12

May effect osteoblast function/activity
Low serum B12 associated with  BMD,  bone loss, 

fracture in most human studies

Supplementation with B12 and folate in CVA

population  hip fracture risk (RCT)

Fish, shellfish, meat, poultry, eggs, milk
Be alert to states associated with  B12

– Vegan – Pernicious anemia – Gastric bypass – Atrophic gastritis (up to 40% elderly) – Celiac, Crohn’s, other GI disease

Sources Bottom Line Relationship to Skeleton The Issues

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Vitamin C

Required for collagen crosslinking
Deficiency state (scurvy)—defective collagen matrix, 

bone resorption, osteoporosis, fractures

 serum levels common in elderly, institutionalized
Smoking  intestinal absorption, increases catabolism
 Vit C intake associated with  BMD,  bone loss, 

fractures

Fresh fruits and vegetables
Low with tobacco, EtOH
Malabsorptive states
Ensure fresh fruit/veg intake in at risk individuals

Sources Bottom Line Relationship to Skeleton The Issues

Vitamin K

Co-enzyme for carboxylase enzyme
Carboxylated osteocalcin attracts Ca, enhances

mineralization

Undercarboxylated osteocalcin associated with  bone

resorption, fracture

Low serum Vit K assoc with lower BMD,  fracture risk
Intervention studies mixed: BMD neg, fx +
K1: Broccoli, cabbage, spinach, brussel sprouts, turnip

greens, lettuce, vegetable oils; K2: meat, eggs, dairy, natto (ferm soy)

Many veg’s good sources both Vit K and Ca
May be issue in malabsorption, chronic antibiotic use
2 Viactiv chews = 80 mcg (DRI ~90-120 mcg)
MK4 used as osteoporosis therapy in Japan

Sources Bottom Line Relationship to Skeleton The Issues