Nutrition: Beyond Calcium and Vitamin D Deborah E. Sellmeyer, MD - - PowerPoint PPT Presentation

Page 1

Nutrition: Beyond Calcium and Vitamin D

Deborah E. Sellmeyer, MD Professor of Medicine Division of Endocrinology, Gerontology, and Metabolism Stanford University 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?

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.

Page 2 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

KCitrate and Long-term Calcium Balance

• Randomized (stratified by gender) to 6 months of:

– Placebo (n=18) – Potassium citrate 60 mmol/day (n=18) – Potassium citrate 90 mmol/day (n=17)

• NAE Western diet = 50-75 mmol/day
• Baseline and Month 6

– 12 days controlled diet – Calcium balance: days 7-12 complete urine and stool collections in 24 hour increments = dietary calcium intake – (urine calcium + fecal calcium) – Fractional calcium absorption (oral / IV stable isotopes)

Study Procedures

• Dietitian counseled and monitored self-selected

diet to 600 mg/d

• Calcium and vitamin D

– 600 mg dietary calcium – 630 mg calcium citrate – 400 IU vitamin D

• Two week run-in

– Calcium 1230 mg/d (diet + supplements) – Vitamin D 400 IU/d – Placebo (identical to KCitrate): 3 pills, 3 times / day

Page 3 Subject Characteristics

Placebo (n=18) K Citrate 60 mmol/day (n=17) K Citrate 90 mmol/day (n=17) Age (years) 65.2 + 6.2 64.7 + 5.9 63.8 + 6.4 Gender (% female) 67% 67% 73% Race (% Caucasian) 83% 100% 78% BMI (g/m2) 26.0 + 4.0 25.1 + 2.7 24.3 + 3.3 Urine calcium (mg/day) 184 + 59 206 + 94 189 + 82 25-hydroxyvitamin D (ng/ml) 36 + 10 31 + 10 32 + 10 No significant differences at baseline.

Net Acid Excretion

*p<0.05 compared to placebo 40 30 20 10

• 10
• 20
• 30

* *

• 40

Net acid excretion (meq/day) Placebo KCitrate 60 mmol/day KCitrate 90 mmol/day

NAE = (Titratable Acid + NH4) – HCO3

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.

Page 4 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 (%)

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

Page 5 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

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

Page 6 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

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

Page 7 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

Summary

• No fracture data; minimal BMD data
• Protein

– Ensure adequate protein intake (0.8 g/kg/day) – Soy/isoflavones

• great vegetarian protein source
• great calcium source
• interest diminishing for isoflavones for bone
• Robust intake of fruit/vegetables (4 cups women,

5 cups men)

• Limit sodium chloride
• Be aware of particular conditions associated with

deficiencies/excesses of trace minerals, vitamins

Questions?