Milk Avoidance and Milk Lactose maldigesters are lactose intolerant - - PowerPoint PPT Presentation

Milk Avoidance and Milk Alternatives

Dennis Savaiano, PhD Virginia C. Meredith Professor of Nutrition Science Purdue University savaiano@purdue.edu

The traditional dogma:

• Lactose maldigesters are lactose intolerant
• They need to avoid milk
• Use digestive aids
• Take supplements
• Eat low lactose alternatives
• Don’t worry about lower calcium intakes and

poor bone health

Reality of the science

• Perceived lactose (milk) intolerance causes

milk avoidance

• Milk avoidance causes low CA intakes and

poor bone health

• Lactose maldigestion is easily managed with

regular single servings of milk with meals

Increased fracture rate

Lactose Intolerance (real or perceived) 5 - 40%

• f maldigesters

Low Calcium intake

• 200 to -300 mg/day

Low BMD Scientific reality

Dietary Management of LM

• Dose
• Timing of dose
• Colon adaptation
• Residual mammalian lactase
• Food sources vary in lactose
• Meal feeding and lactose intolerance
• Psychological factors (learned aversion)

Intolerance vs. maldigestion

• Self described intolerant, n=30
• 21 maldigesters, 9 digesters
• Randomized, double blinded
• Milk vs Lactose hydrolyzed milk
• One cup (12g lactose) with breakfast daily for
• ne week

NEJM 333(1):1-4, 1995

Self-described intolerant maldigesters, n=21

Symptom Milk Hydrolyzed Milk Difference 95% CI Bloating # 0.6 +/- 0.1 0.5 +/- 0.1 0.1 +/- 0.1

• 0.2 to 0.4

Abdominal pain # 0.4 +/- 0.1 0.3 +/- 0.1 0.1 +/- 0.1

• 0.1 to 0.3

Diarrhea (episodes/day) 0.1 +/- 0.0 0.3 +/- 0.1

• 0.2 +/- 0.1
• 0.4 to 0.0

Flatus severity# 1.1 +/- 0.1 0.9 +/- 0.1 0.2 +/- 0.1 0.0 to 0.4 Flatus (episodes/day) 10.1 +/- 1.5 7.6 +/- 1.2 2.5 +/- 1.1 0.2 to 4.8

# 0 to 5 ranking of symptoms: 0 none, 1 trivial, 2 mild, 3 moderate, 4 strong, 5 severe

Self-described intolerant digesters, n=9

Symptom Milk Hydrolyzed Milk Difference 95% CI Bloating # 0.6 +/- 0.2 0.5 +/- 0.2 0.2 +/- 0.2

• 0.3 to 0.7

Abdominal pain # 0.6 +/- 0.2 0.4 +/- 0.2 0.2 +/- 0.1 0.0 to 0.4 Diarrhea (episodes/day) 0.3 +/- 0.2 0.2 +/- 0.1 0.1+/- 0.2

• 0.4 to 0.6

Flatus severity# 0.9 +/- 0.2 1.2 +/- 0.2 0.3 +/- 0.2

• 0.2 to 0.8

Flatus (episodes/day) 11.8 +/- 2.3 8.4 +/- 1.9 3.4 +/- 1.7

• 0.53 to 7.3

# 0 to 5 ranking of symptoms: 0 none, 1 trivial, 2 mild, 3 moderate, 4 strong, 5 severe

Tolerance to two cups of milk

• Self-reported intolerant
• One cup with breakfast and one with dinner
• Very modest increase in symptoms with

lactose vs. hydrolyzed milk

• Self-reported intolerants systematically

reported more symptoms regardless of the lactose content of the milk

AJCN 65: 1502-6, 1997

Five servings of dairy per day = 1500mg Calcium

(Suarez et al 1998) Symptom Baseline Lactose Hydrolyzed Conventional Excessive gas Maldigesters 0.5 +/- 0.1 a 0.8 +/- 0.2 a 1.3 +/- 0.2 b Digesters 0.4 +/- 0.1 0.4 +/- 0.1 0.4 +/- 0.1 Bowl movements Maldigesters 1.3 +/- 0.1 a 1.6 +/- 0.2 b 1.8 +/- 0.2 c Digesters 1.3 +/- 0.1 1.4 +/- 0.1 1.3 +/- 0.1 Diarrhea Maldigesters 0.02 +/- 0.02 0.11 +/- 0.08 0.17 +/- 0.09 Digesters 0.07 +/- 0.05 0.07 +/- 0.04 0.02 +/- 0.01 Total flatus Maldigesters 10.6 +/- 2.0 a 10.7 +/- 1.3 a 17.1 +/- 2.1 b Digesters 13.7 +/- 1.9 12.8 +/- 1.5 14.7 +/- 1.9

Meta analysis to estimate the occurrence of lactose intolerance in blinded and controlled studies:

• Cross over designs with lactose-free or low lactose

product

• Physiological dose (< 25g)
• Blinding
• Symptoms reported by frequency or occurrence
• Subjects > 4 years of age

J Nutr 2006:136:1107-1113

• 1553 citations from MEDLINE under MeSH

heading of LI 1/96 – 1/02

• 108 identified as related to the primary aim with

‘healthy’ subjects

• 53 additional articled identified from secondary

literature

• Overall 21 studies eligible for inclusion based on

the criteria

• 11 studies reported ‘severity’ of symptoms

Lactose Tolerance

GI Transit Effect Diet Lactose Residual Lactase Activity Colonic Fermentation Summary: GI physiology

Summary: dietary management

• Lactose intolerance is dose related
• One serving of milk is typically well tolerated

with a meal

• Many dairy foods are well tolerated (yogurts)
• Colon adaptation significantly improves

lactose tolerance

• Lactose intolerance should not be an

impediment to adding dairy foods to the diet

Perceived Milk Intolerance Is Related to Bone Mineral Content in 10- to 13-Year-Old Female Adolescents-Matlik et al 2007

• 258 girls completed the Perceived Milk Intolerance

questionnaire ( 10-13 yrs of age)

• 230 girls completed breath hydrogen testing
• 28% Asian, 33% Hispanic, 39% non-Hispanic

white

• 43% were maldigesters
• 47 considered themselves to be milk intolerant

20 were maldigesters, 22 were digesters.

Perceived Lactose Intolerance

Lactose Challenge Questionnaire 1.) I am allergic to milk 2.) Milk makes my stomach hurt after I drink it 3.) I have been told that milk will make my stomach hurt after I drink it Strongly Disagree (1) Strongly Agree (5) Do Not Know (0)

Perceived and true lactose intolerance Perceived and true lactose intolerance

Asian Hispanic Non- Hisp White Total

n (%)

Completed PLI questionnaire 47 (64) 77 (79) 92 (76) 216 (74) Positive for PLI 11 (23) 12 (15) 20 (21) 43 (20) Positive for LI 1 (1.5) 5 (6.6) 5 (5.6) 11 (4.8)

Lactose Maldigestion (LM) Results

30.8% 69.2% 48.7% 51.3%

Asian Participants n=65 Hispanic Participants n=76

84.3% 15.7%

Digester Maldigester

Non-Hispanic White Participants n=89

2=47.489, df=2,P<.0001 LM LM LM

Dependent Variables Lactose Digestion Coefficient (95% CI) 1 P-value Total food calcium (mg)

• 6 ± (-184 to 172)

.945 Dairy calcium (mg) 9 ± (-121 to 139) .889

Dietary calcium intake was not related to lactose maldigestion status.

1Lactose digester coded as 1, Lactose maldigester coded as 0. Thus, negative indicates lower

intake among lactose digesters. Adjusted for location (state), race/ethnic group, weight, and age.

Matlik et al. Pediatrics Sept 2007

Dependent Variables Lactose Digestion Coefficient (95% CI) 1 P-value Total body BMC (g) 30.88 (-45.01 to 106.82) .424 Spine (L2-L4) BMC (g)

• 0.12 (-1.94 to 1.71)

.898 Total hip BMC (g) 0.21 (-0.83 to 1.26) .689 Femoral neck BMC (g) 0.078 (-0.08 to 0.23) .317

Bone status as BMC was not related to lactose maldigestion status.

1Lactose digester coded as 1, Lactose maldigester coded as 0. Thus, negative indicates lower

value among lactose digesters. Adjusted for location (state), race/ethnic group, BMI, Tanner score and age.

Matlik et al. Pediatrics Sept 2007

Dependent Variables PMI Coefficient (95% CI)1 P-value Total food calcium (mg)

• 212 (-394 to -29)

.023 Dairy calcium (mg)

• 168 (-303 to -34)

.015 Non-dairy calcium (mg)

• 23 (-61 to 14)

.222 Total dairy (dairy + mixed) (mg)

• 188 (-352 to -24)

.025 Servings of milk (cups/day)

• 0.48 (-.82 to -.14)

.006

Dietary calcium intake was related to perceived milk intolerance.

1Positive for perceived milk intolerance coded as 1, no perceived milk intolerance coded as 0. Thus

negative is lower intake among PMI. Adjusted for location (state), race/ethnic group, weight, and age.

Matlik et al. Pediatrics Sept 2007

Dependent Variables PLI Coefficient1 P-value Total body BMC (g)

• 69.65 (-147.7 to 8.5)

.080 Spine (L2-L4) BMC (g)

• 2.52 (-4.4 to -.64)

.009 Total hip BMC (g)

• 0.95 (-2.05 to 0.15)

.089 Femoral neck BMC (g)

• 0.14 (-0.3 to 0.02)

.083

Bone status as BMC was related to perceived milk intolerance.

1Positive for perceived lactose intolerance coded as 1, no perceived lactose intolerance coded

as 0. Thus negative values indicate lower bone values among girls positive for PMI. Adjusted for location (state), race/ethnic group, BMI, Tanner score and age.

Matlik et al. Pediatrics Sept 2007

Improving milk intake in milk- averse lactose digesters and maldigesters

Lauren O’Connor, Tracy K Eaton and Dennis A Savaiano JNEB 47:4:325-330

Inclusion criteria

• 18-55 years old
• Aversion to milk for at least 1 year
• Only incidental consumption of milk for at

least 6 months

Exclusion criteria

• Milk allergy
• Chronic GI illness
• Chronic heartburn
• Stomach ulcers
• Colon cancer
• Gastroesophageal reflux disease
• Pregnancy
• Tobacco use
• Antibiotic use within the past 2 months

Recruitment

Milk Introduction protocol Change in aversion and consumption

Baseline Average 3 Month Average p 6 Month Average p Aversion Score (higher = less aversion) 42.50 63.65 0.001 57.17 0.0345 Likeness Score (higher = like)

• 1.62
• 0.38

0.000

• 0.48

0.000 Milk Consumption (servings/month) 0.31 10.23 0.000 5.91 0.000 BCAT Score* 18.23 32.65 0.000 26.96 0.0125

Milk Consumption Frequency at 3 Months

Digesters Maldigesters Total Top milk drinkers (>1 serving per week) 10 8 18 Bottom milk drinkers (<1 serving per week) 5 3 8 Total 15 11 26

Symptom scores during HBT

0.05 0.1 0.15 0.2 0.25 0.3 0.35

• 15

30 60 120 180 240 300 Symptom score average time (minutes) during hydrogen breath test

Lactose Maldigesters during HBT*

baseline day 22

Symptom average scores during HBT

0.02 0.04 0.06 0.08 0.1 0.12 0.14 0.16 0.18 0.2

• 15

30 60 120 180 240 300 Overall Symptom Average Score Time (minutes)

Lactose Digesters during HBT*

baseline day 22

Take home lessons

• Subjects increased milk consumption to

approximately 1/3 serving per day at 3 months (100mg CA per day)

• Milk consumption and calcium intakes

remained low at 3 and 6 months

• Symptoms of lactose intolerance were low

throughout the study

• Little or no difference in adaptation between

digesters and maldigesters

Adult population w/ milk avoidance-1 Adult population w/ milk avoidance-1

Author N Age Gender Race / ethnicity Perceived Lactose Intolerance Ca2+ Bone Harris 1982 8749 0-66+ MF Britain 6.3% limited/avoided 1.4% due to LI Honkanen 1996 2025 48-59 F Finland 8% PLI

• 270

mg/d ↓femoral & spinal BMD Honkanen 1997 11,619 47-56 F Finland 7.7% self-reported LI

• 280

mg/d ↑ fracture Carroccio 1998 323 5-85 MF Sicily 15.1% self-reported LI LM LD nd

• 265

mg/d Klesges 1999 32,144

17-35 MF

US Air Force 16.1% perceived milk- related gastric distress ↓ dairy Elbon 2000 475 60-89 MF US AA White 16-21% PMI ↓ dairy

Adult Population w/ milk avoidance-2 Adult Population w/ milk avoidance-2

Author N Age Gender Race / ethnicity Perceived Lactose Intolerance Ca2+ Bone

Enattah 2005

453 62-78 F Finland 16% self-reported LI

• 260

mg/d dairy

Lovelace 2005

159 19-87 MF Canadian All with PLI 591mg-food 746mg- supplements

Krull 2009

367 25-70 MF Estonia 11.7% self-reported LI ↓50% milk Nicklas 2011 3452 >18 MF US 12.3% self-perceived LI

• 211

mg/d Barr 2013 2251 >18 MF Canadian 16% self-reported LI

• 154

mg/d Casellas 2016 580 29-52 MF Spain GI referrals for LI 56% self-perceived LI 91% PLI restricted dairy Zingone 2017 1173 18-75 MF Italy 22.2% avoided milk 18.1% drink lac-free

Clinical studies of milk avoidance Clinical studies of milk avoidance

Author N Age Gender Race / ethnicity Perceived Lactose Intolerance Ca2+ Bone Corazza 1995 58 57+/- 7 PMF Italy PLI and tested LI

• 220

mg/d ↓BMD Buchowski 2002 50 35 +/- 7 F US African American LM 26 LI among LM

• 393

mg/d Stefano 2002 103 25-33 MF Italy 32 PLI, 55 LM 29/55 LI

• 240

mg/d LI ↓BMD w/LI Segal 2003 66 20-78 MF Israel LM and LI ↓dairy ↓BMD to ref Obermeyer- Pietsch 2004 258 62 +/-9 PM F Austria 23.6% LCT CC 26% of these disliked milk ↓milk by 50% Gugatschka 2005 208 56+/- 12 Austria 14.9% avoided milk

• 117 mg/d

Casellas 2016 580 29-52 MF Spain GI referrals for LI 56% PLI 91% PLI ↓dairy

Sumary: Lactose intolerance and the risk for osteoporosis

• PLI is a barrier for CA consumption in some

maldigesters (and even some digesters)

– 5% to 40% ? – 200 to 300mg per day lower intake

• Lower BMD with long-term lower CA

consumption in both young and older women

• Increased fracture rate

– non-ankle lower body

Alternative beverages

• Carbonated beverages
• Lactose-free milk
• Plant-based milks

Low lactose milks

Plant-based milks

• Sales growing double digits per year
• Almond milks sales have surpassed soy milks
• Still a small segment of the market
• Many new products/formulations
• Nutrient composition can vary dramatically
• Plant-based diet focus
• Anti-dairy/lactose intolerance argument
• Sustainable agriculture focus

Plant-based ‘milks’

Nutrient variability in plant-based beverages- 1 cup

Product Calories Fat (g) Carb (g) Na (mg) K(mg) Pro(g) Ca(mg) D(IU) 1% milk 110 2.5 12 125 401 8 300 101 Ripple Pea 133 5.3 15.3 121 360 8 466 121 Silk Cashew 82 2.4 13.5 190 31 0.7 305 94 Silk Cashew 24 2 1 161 24 1 451 101 Numoo Pistachio 113 5.3 16.7 134 233 2.7 34 BD Almond 28 2.6 1.5 175 175 0.7 437 102 BD Almond Coconut blend 70 3 10 125 161 3 451 101 BD Almond Chocolate 159 4 30 211 332 2 601 140 Soy Dream 120 4 14 134 360 7 350 101 WF Soy milk 79 4 4 84 300 7 300 120 Eden Soy 149 3 23 91 310 7 199 41 USDA ARS Database

The Truth About Calcium and Osteoporosis

• T. Colin Campbell Center for

Nutrition Studies China Report: Osteoporosis

Drivers of choice (McCarthy et al 2017)

• Tastes good
• Natural
• Healthy
• Organic
• Reduced fat
• Vitamin fortified
• Protein
• Tastes good
• Healthy
• Weight control
• GH free
• Digestive benefits
• Natural
• Organic
• Vitamin fortified
• Ca equal to milk
• Protein equal to milk

Milk drinkers Plant-based beverage drinkers

Conjoint analysis: key factors and levels

Attribute Fluid milk Nondairy Fat content (%) 26.9 a 15.2 c Package size 18.6 b 16.7 b Label claims 16.7 c 7.1 d Shelf life 15.2 d na Milk type 7.1 f na Sugar level na 26.9 a Plant source na 18.6 b Protein content 9.1 e 9.1 d Brand 6.4 f 6.4 e

Must reads

• National Institutes of Health Consensus Development Conference: Lactose

Intolerance and Health, February 2010

– http://www.annals.org/cgi/content/full/0003-4819-152-12-201006150-00248v1 – http://consensus.nih.gov/2010/lactoseabstracts.htm#Tishkoff

• LI in Infants, Children and Adolescents. MB Heyman for the Committee on
• Nutr. Pediatrics 2006

– http://www.pediatrics.org/cgi/content/full/118/3/1279

Closing thoughts

• It is not reasonable to expect fluid milk

consumption to increase in the US

• Global markets have much upside potential
• Plant-based diets will likely become more

common in developed countries

• Is the current US animal production industry

sustainable?

Questions Loss of Lactase Activity

• Lactase non-persistence (primary acquired):

Genetically programmed loss of lactase post-weaning after weaning.

• Secondary acquired: Temporary loss due to

illness, medication, radiation.

• Congenital lactase deficiency: Complete absence
• f lactase at birth (rare).

Prevalence of Lactase Non-persistence

Ethnic Group % of Adults Northern European 1-5 Middle European (English, Russian) 10-20 Mexican-American 50-80 Mediterranean (Greek, Italian) 60-90 Most African and African-American 70-100 Native American 80-100 Asian and Asian-American 80-100

Adapted from: Savaiano, DA and Levitt MD. Milk intolerance and microbe-containing dairy foods. J Dairy Sci 1987; 70: 397-406

• U. S. Population 2025

U.S. Department of Commerce estimates

253M White x 20% LM = 47M 43M Black x 75% LM = 32M 19M Other x 100% LM = 19M 298M Total/98M= 33%LM

World Population and Lactose Maldigestion Projections

Population Estimates: United Nations

%LM 1995 (LM) 2000 (LM) 2025 (LM) Africa

75 753M (565) 877M (658) 1642M (1231)

Asia

100 3299 (3,299) 3543 (3543) 4466 (4466)

Europe

20 809 (162) 827 (165) 893 (179) Latin America 70 501 (351) 550 (385) 786 (550) North America 25 286 (72) 297 (74) 347 (87)

Oceania

25 28 (7) 30 (8) 39 (10)

World

5679 (4,456) 6127 (4833) 8177 (6523) 78% 79% 80%

Digesters and maldigesters are two populations

Rossi M. et al., Gastroenterology (1997) 112:1506-1514

p ersistent h ypo lactasics

lactase activity/protein (U/g)

10 20 30 40 50

N=10 N=34

Secondary lactose intolerance

• A major concern in some regions/populations
• Recurrent abdominal pain

– Mixed data

• IBS
• Cow’s milk allergy recovery
• Acute gastroenteritis
• HIV
• Protein Energy Malnutrition

Colon Adaptation AJCN 1996:64:232-6 Discussion- Contributions to the literature Discussion- Contributions to the literature

Author N Age Gender Race / ethnicity PLI Ca2+ Bone

DiStefano 2002

103 25-33 M & F Italian 31% reported lactose intolerant LILM’s had significantly lower calcium intake than LM’s with no symptoms LILM’s had significantly lower lumbar spine and femoral neck T-scores and z-scores

Honkanen 1997

11,619

38-57 F Finnish 7.7% reported lactose intolerant PLI consumed significantly less calcium than non- PLI 1299 reported fractures. Fractures at tibia and metatarsal strongly related to PLI

Corazza 1995

58 Post MP Mean age 58 Italian 32.7% perceived lactose intolerant LI calcium intake <400 mg/day compared to LD calcium intake of >600mg BMD lower in LILM’s compared to LD

Discussion- Contributions to the literature Discussion- Contributions to the literature

Author N Age Gender Race / ethnicity PLI Ca2+ Elbon 1999 475 60-89 M & F AA White 17.7% perceived milk intolerance PLI were more likely to “not try at all” to consume enough calcium. PLI’s were more likely to consume milk less than once per month during adolescence and currently Klesges 1999

32144

17-35 M & F NHW AA Asian Hisp Other 16.1% perceived milk-related gastric distress PLI’s averaged 1.03 fewer servings of milk per day Carroccio 1998 323 5-85 M & F Sicilains 15.2% self- reported milk intolerance PLI reported significantly less calcium (320 mg/day) than LT individuals (585 mg/d). Calcium also lower in 11 true LI adults compared to others without symptoms

Food item Percentage

• f NNR in

100 g product Number of nutrients ≥ 5% of NNR Nutrient density GHG emission NDCI index Milk 126 9 53.8 99 0.54 Soft drink 7 109 Orange juice 90 4 17.2 61 0.28 Beer 18 101 Red wine 24 1 1.2 204 0.01 Mineral water 2 10 Soy drink 53 3 7.6 30 0.25 Oat drink 32 1 1.5 21 0.07

Nutrient density in relation to climate impact (Smedman et al 2010)