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Advanced Nutrition
Mineral Nutrition
Calcium
in Health and Disease Prevention
MargiAnne Isaia, MD MPH
Mineral Nutrition
Calcium in Health and Disease Prevention
Calcium and Bone Health
No clear disorder of intra-cellular Calcium regulation
Cell injury, damage, serious dysfunction – always associated with a rise
in cytosolic Ca concentration – cell death
Low Ca intake, high Ca losses from the body – osteoporosis
During growth:
- high demands of skeletal mineralization
- extremely low-Ca diets lead to hypocalcemia
- this is followed by hyper secretion of PTH with low serum P
(undermineralization of the newly deposited bone matrix and
osteoblast dysfunction = rickets)
Nutritional hypo Ca – in Mg deficiency:
severe alcoholism, intestinal fistula, malabsorption
Both, PTH release from PT glands and bony response to PTH are
dependent on Mg; both are defective in Mg deficiency
Mineral Nutrition
Calcium in Health and Disease Prevention
Calcium and Bone Health
Osteoporosis = the most common disorder of Ca metabolism
involves regulation of ECF [Ca 2+]
Characteristics: loss of bone mass (decreased bone mass/unit volume)
micro architectural deterioration of bone tissue
increased risk of fracture
Causes for osteoporosis:
- reduced Estrogen levels after menopause
- dietary Ca deficiency
- physical inactivity
- excessive alcohol use
- underweight
- hereditary factors ( white women > risk than black women)
- secondary to pathologic conditions: hyperthyroidism, hyperPTH,
premature menopause (before age 42), hypogonadism in men
(testosterone deficiency), chronic lung disease, Cushing’s disease, long
term use of CS drugs or Heparine
Mineral Nutrition
Calcium in Health and Disease Prevention
Calcium and Bone Health
Osteoporosis Diagnostic Standards
WHO Consensus Conference
Bone Mineral Density BMD
Normal
< 1 SD below reference
Osteopenia 1 – 2.5 SD below reference
Osteoporosis > 2.5 SD below reference
Mineral Nutrition
Calcium in Health and Disease Prevention
Calcium and Bone Health
Bone architecture
Revision of bony material
Bone mass in adults is maintained locally by
the balance between osteoclastic bone formation
and osteoblastic bone formation
Bone resorption and formation are “coupled”
locally: when one goes up or down
the other usually follows
Resorption is much faster than formation:
it takes at least 3 months to rebuild bone
resorbed in 2-3 weeks
Mineral Nutrition
Calcium in Health and Disease Prevention
Calcium and Bone Health
Hormones and Bone Health
Calcium regulating hormones:
Parathyroid hormone PTH
Calcitriol ( 1,25 dihydroxy Vitamin D3)
Calcitonin- blocks bone resorption
Sex hormones:
Estrogen- acts on osteoclasts to inhibit bone resoption
-acts on osteoblasts to stimulate bone formation
Testosterone – stimulates bone formation and muscle growth
Other systemic hormones
Growth Hormone – regulator of skeletal growth
stimulates production of IGF-1
Thyroid hormone – increases energy production of all cell
Cortisol – large amount blocks bone growth (CS therapy)
Insulin & Leptin – anabolic effect
Mineral Nutrition
Calcium in Health and Disease Prevention
Calcium and Bone Health
Humoral factors acting on bone cells
Osteoblasts:
Osteoclasts:
PTH
1,25 dihydroxy Vitamin D
Glucocorticoids
Insulin-like Growth Factor (IGFs)
Transforming Growth Factor b (TGF-b)
Parathyroid hormone-related peptide (PTHrP)
Osteoprotegerin (OPG) or
Osteoclastogenesis inhibitory factor (OCIF)
Calcitonin
Bisphosphonate drugs
Interleukin -1
Colony-stimulating factor-1 (CSF-1)
Transforming Growth Factor a (TGF-a)
Transforming Growth Factor b (TGF-b)
Gallium nitrate
Mineral Nutrition
Calcium in Health and Disease Prevention
Calcium and Bone Health
Effect of age on hormonal influences
PTH
levels hwith age
Growth Hormone and IGFs
iwith age
Vitamin D
ioutdoor activity
isynthesis by skin
icalcitriol synthesis (kidney)
iintestinal response
Sex hormones
iwith age
Mineral Nutrition
Calcium in Health and Disease Prevention
Calcium and Bone Health
Forms of Osteoporosis
Type I - post-menopausal, loss of trabecular bone, women
Type II – senile, loss of trabecular and compact bone, men and women
Postulated mechanisms:
Type I
iEstrogen
iBone formation & hbone resorption
ibone volume
hserum Calcium
iPTH (2nd hypoPTH) & hurinary Ca
i1, 25 dihydroxy Vitamin D
iCa absorption
Type II
i1,25 dihydroxy Vitamin D
iCa absorption & ibone formation
(local gut conditions)
iserum Calcium
hPTH (2nd hyper PTH)
hbone resorption
ibone volume
Mineral Nutrition
Calcium in Health and Disease Prevention
Calcium and Bone Health
Osteoporosis – Diagnostic
Patient history and physical examination
Bone density scan (DEXA)
Blood or urine tests
Routine X-rays do not detect osteoporosis until 25%
or more bone mass has been lost
Mineral Nutrition
Calcium in Health and Disease Prevention
Calcium and Bone Health
Physical Examination Tests
for detection of Occult Vertebral Fractures:
A. Wall-Occiput Test
for Occult Thoracic Vertebral Fractures
(+): being unable to touch the wall with the occiput
when standing with the back and heels against the wall
and the head positioned such as
an imaginary line from the lateral corner of the eye to the
superior junction of the auricle is parallel to the floor
B. Rib-Pelvis Distance Test
for Occult Lumbar Vertebral Fractures
(+): the distance of less or equal to two finger breadths
between the inferior margins of the ribs and the superior
surface of the pelvis in the mid-axillary line
Mineral Nutrition
Calcium in Health and Disease Prevention
NUTRITION
HORMONES
EXERCISE
BONE MASS
BONE
ARCHITECTURE
LIFESTYLE
FACTORS
FLEXIBILITY
BONE
STRENGTH
Mineral Nutrition
Calcium in Health and Disease Prevention
Calcium and Bone Health
Nutritional Determinants of Bone
The bone mineral: hydroxyapatite Ca 10 (PO4)6 (OH)2
Ca, Phosphate, Magnesium, other minerals
Boron intake - decreases urinary excretion of Ca, P, Mg
- increases serum Estradiol
It is postulated that Boron is necessary for formation of certain
steroid hormones or hydroxylation of 25(OH) D
Strontium - proposed as an agent for improving BMD
(studies in Europe in postmenopausal women)
Manganese, Zinc and Cooper – cofactors for enzymes essential to bone tissues
Mineral Nutrition
Calcium in Health and Disease Prevention
Calcium and Bone Health * * Nutritional Determinants of Bone
Protein – sufficient in the diet to form adequate bone collagen matrix
Increased protein in the diet – increased absorption of Ca
- increased urinary Ca loss
The overall acid-base balance of the diet will influence the impact
of dietary protein on bone:
a high intake of alkaline foods (fruits & vegetables)
-may mitigate the calciuric effect of protein
-may promote a net positive impact of Phosphorus on the
skeleton
Vitamin D
Vitamin K serves as co-enzyme in the g-carboxylation of glutamic
acids residues on protein
3 vitamin K dependent proteins in the bone:
Osteocalcin - synthesized by osteocytes and binds to free Ca
and to hydroxyapatite (70% of Osteocalcin is incorporated in
bone matrix; 30% is found in the blood- its level is indicator
for new bone formation
Matrix gla protein
Protein S
CALCIUM CONTENT OF SELECTED VEGAN FOODS
Food
Amount
Calcium (mg)
Blackstrap molasses
Collard greens, cooked
Tofu, processed with calcium sulfate
Calcium-fortified orange juice
Soy or rice-milk, commercial,
calcium-fortified, plain
Commercial soy yogurt, plain
Turnip greens, cooked
Tofu, processed with nigari
Tempeh
Kale, cooked
Soybeans, cooked
Okra, cooked
Bok choy, cooked
Mustard greens, cooked
Tahini
Broccoli, cooked
Almonds
Almond butter
Soy milk, commercial, plain
2 Tbsp
1 cup
4 ounces
8 ounces
400
357
200-330
300
8 ounces
6 ounces
1 cup
4 ounces
1 cup
1 cup
1 cup
1 cup
1 cup
1 cup
2 Tbsp
1 cup
1/4 cup
2 Tbsp
8 ounces
200-300
80-250
249
80-230
215
179
175
172
158
152
128
94
89
86
80
Mineral Nutrition
Calcium in Health and Disease Prevention
Calcium and Bone Health
Prevention of Osteoporosis
Healthy diet:
Adequate intake of bone supporting nutrients:
Ca, vitamin D, protein and vitamin K
DRI 50-70 y 1200 mg Ca and 10 mcg (400 IU)
> 70 y 1200 mg Ca and 15 mcg (600 IU)
Vitamin D 1 mcg = 40 IU
Avoid excess intake of P, vitamin D, protein, Sodium
Avoid caffeine and alcohol
Lifestyle
Avoid smoking
Reduce risk of falling
Increase weight-bearing activity – 20 minutes 7x/week
(stabilization of bone mass) for post menopausal women
Increase muscle-strengthening exercises – 30-40 minutes 7x/week
(help stabilize bone density) for post menopausal women
Mineral Nutrition
Calcium in Health and Disease Prevention
Calcium and Bone Health
Prevention of Osteoporosis
Particularly important to consume adequate Ca and Vitamin D
throughout infancy, childhood, adolescence
Kid’s bones:
A study of girls showed that average Calcium intake 500-1500 mg/d
from 12-18 years of age was not associated with hip bone density at age 20,
or with total bone mineral gain during the teen years.
However, achievable levels of exercise and fitness have a favorable effect on bone.
In the adult life:
Engage in weight-bearing exercise to maximize bone strength and
bone density to help prevent osteoporosis later in life
Weight-bearing exercises – bones and muscles work against gravity
while they bear your weight :
walking, running, aerobics, skating
Non-weight bearing exercises: swimming, bicycling, water aerobics
Mineral Nutrition
Calcium in Health and Disease Prevention
Calcium and Bone Health
Prevention of Osteoporosis
WHO Recommendation: Ca 500-600 mg/d
“ The accumulated data indicate the possibility that the
adverse effect of protein, in particular animal protein,
might outweigh the positive effect of Calcium intake on
Calcium balance.
Instead, increase physical activity, reduce Na intake and
animal protein intake and increase the consumption of
fruit and vegetables”.
Mineral Nutrition
Calcium in Health and Disease Prevention
Calcium and Bone Health - - Osteoporosis-medications
Estrogen – directly influence bone turnover
enhances Ca absorption through its trophic effect on 1,25,(OH)2D
When administered to post menopausal women, E lowers the bone remodeling rate
and retards bone loss
Risk: MI, stroke, Breast Cancer, Pulmonary Emboli, DVT
FDA: hormone therapy to be used in the lowest possible dose,
for the shortest duration
- given with Progestin, if no hysterectomy
If for the treatment of Osteoporosis alone, non-Estrogen treatment considered first
Bisphosphonates ( Alendronate, Risendronate)
structural analogues of pyrophosphate
Inhibition of hydroxyapatite formation & bone resorption inhibition
Special requirements for administration
Side effects: upper GI symptoms
Calcitonin- primary function to inhibit bone resorption
Women with osteoporosis have an attenuated Calcium response to a Ca challenge
Raloxifene – Selective Estrogen Receptor Modulator
FDA approved for prevention and treatment of osteoporosis
side effects: risk of DVT, accentuated hot flashes
Parathyroid hormone (1-34) or Teriparatide
not approved for use > 2 y
Mineral Nutrition
Calcium in Health and Disease Prevention
Calcium and Prostate Cancer
High Calcium intake appears to be down-regulating the production
of active forms of Vitamin D
Vitamin D is protective of the prostate
High Calcium 2000 mg/day and/or dairy intake > 2.5 servings
may be associated with the development of Prostate Cancer
Calcium from cow’s milk and Prostate Cancer
Insulin-like Growth Factor 1 (IGF-1) may potentiate cancer growth
IGF-1 in milk help the baby grow;
after growing process is ready, IGF-1 negative effect
Milk drinking increases the human IGF-1 secretion
IGF-1 and Prostate Cancer study:
Cancer patients IGF-1 – 269.4 ng/ml , healthy controls – 248.9 ng/ml
Relationship between Ca intake –dairy intake and PC risk remains
unclear.
Recommendation for men >19y Ca 1000- 1200 mg/d
- intake below the upper tolerable limit (2500 mg/d)
Mineral Nutrition
Calcium in Health and Disease Prevention
Cow’s milk intake and Type I Diabetes
1 or more dairy proteins from cow’s milk spark an auto-immune reaction
with damage on pancreatic b-cells
reason why American Academy of Pediatrics warns against
early introduction of cow’s milk
Auto-immune diseases: T1DM, Multiple Sclerosis, Rheumatoid Arthritis,
and Celiac Disease correlated with intake of cow’s milk proteins
Casein-milk protein – addictive (Food addiction)
Cow’s Milk Allergy (CMA)
1.2%-17%
Recurrent Otitis Media – more common and more severe in children with CMA
Asthma, allergic rhinitis, dermatitis 3-4 x greater incidence in the children
who had CMA in infancy compared with control group
Cow’s milk intake and Childhood Obesity
Dairy consumption and weight gain in children????
Cow’s milk and Ovarian Cancer
Galactose can affect ovaries, increased IGF-1 (cancer assessed over 10 y)
Mineral Nutrition
Calcium in Health and Disease Prevention
Calcium and High Blood Pressure
Observational and experimental studies indicate that individuals who eat
a vegetarian diet high in minerals (including Ca, Mg, K) and fiber, low in
fat, tend to have reduced blood pressure.
Clinical trials showed that increased Ca intake lowers BP
and the risk of hypertension
DASH – a study which tested the combined effect of nutrients, including
Calcium from food on blood pressure
DASH = Dietary Approaches to Stop Hypertension
a multicenter research trial
effect of three different diets on BP:
- control, “typical American” diet
- high fruits and vegetables diet
- DASH diet: high fruits and vegetables, low fat (dairy)
Of the three diets tested, the greatest decrease in BP with DASH diet
DASH-Sodium study : DASH diet without Sodium restriction same effect on BP as severe Na restriction on the control diet ( Na: 1500 mg /day)
Mineral Nutrition
Calcium in Health and Disease Prevention
Calcium deficiency if:
- inadequate Calcium intake
- decreased Calcium absorption
- increased urinary Calcium loss
Calcium supplementation:
- post-menopausal women
- amenorrheic women and Female Athlete Triad
- Lactose intolerant individuals
- poorly planned Vegan diet
Mineral Nutrition
Calcium in Health and Disease Prevention
Calcium Supplementation
If Calcium supplements required,
bioavailability of Ca citrate > Ca carbonate
Ca bioavailability determined using:
serum Ca,
urinary Ca,
serum PTH
Ca citrate – role in protecting against bone loss
because of a greater PTH suppression
(PTH suppression is critical in maintaining bone)
PTH responsible for age-related bone loss
hPTH g hleaching Ca from bones
References:
5 ICVN, Loma Linda USA, 2008
Modern Nutrition in Health and Disease, Shils, 10th edition
www.pcrm.org
www. Pubmed.org
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